FACEts of mechanical regulation in the morphogenesis of craniofacial structures

Abstract

During embryonic development, organs undergo distinct and programmed morphological changes as they develop into their functional forms. While genetics and biochemical signals are well recognized regulators of morphogenesis, mechanical forces and the physical properties of tissues are now emerging as integral parts of this process as well. These physical factors drive coordinated cell movements and reorganizations, shape and size changes, proliferation and differentiation, as well as gene expression changes, and ultimately sculpt any developing structure by guiding correct cellular architectures and compositions. In this review we focus on several craniofacial structures, including the tooth, the mandible, the palate, and the cranium. We discuss the spatiotemporal regulation of different mechanical cues at both the cellular and tissue scales during craniofacial development and examine how tissue mechanics control various aspects of cell biology and signaling to shape a developing craniofacial organ.

References

[1] Opitz JM. Goethe’s bone and the beginnings of morphology. Am. J. Med. Genet. A., 2004, 126A: 1-8.

[2] Thompson, D. W. & Thompson, D. W. On Growth and Form. (Cambridge University Press, 1917).

[3] Kindberg A, Hu JK, Bush JO. Forced to communicate: Integration of mechanical and biochemical signaling in morphogenesis. Curr. Opin. Cell Biol., 2020, 66: 59-68.

[4] Stooke-Vaughan GA, Campàs O. Physical control of tissue morphogenesis across scales. Curr. Opin. Genet. Dev., 2018, 51: 111-119.

[5] Huycke TR, Eames BF, Kimmel CB. Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone. Development, 2012, 139: 2371-2380.

[6] Wu P, Jiang T-X, Suksaweang S, Widelitz RB, Chuong C-M. Molecular shaping of the beak. Science, 2004, 305: 1465-1466.

[7] Shraiman BI. Mechanical feedback as a possible regulator of tissue growth. Proc. Natl Acad. Sci. USA, 2005, 102: 3318-3323.

[8] Mao Y, . Differential proliferation rates generate patterns of mechanical tension that orient tissue growth. EMBO J., 2013, 32: 2790-2803.

[9] Aegerter-Wilmsen T, Aegerter CM, Hafen E, Basler K. Model for the regulation of size in the wing imaginal disc of Drosophila. Mech. Dev., 2007, 124: 318-326.

[10] Aegerter-Wilmsen T, . Exploring the effects of mechanical feedback on epithelial topology. Development, 2010, 137: 499-506.

[11] Streichan SJ, Hoerner CR, Schneidt T, Holzer D, Hufnagel L. Spatial constraints control cell proliferation in tissues. Proc. Natl Acad. Sci. USA, 2014, 111: 5586-5591.

[12] Pan Y, Heemskerk I, Ibar C, Shraiman BI, Irvine KD. Differential growth triggers mechanical feedback that elevates Hippo signaling. Proc. Natl Acad. Sci. USA, 2016, 113: E6974-E6983.

[13] Bornhorst D, . Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions. Nat. Commun., 2019, 10: 1-10.

[14] Gros J, Scaal M, Marcelle C. A two-step mechanism for myotome formation in chick. Dev. Cell, 2004, 6: 875-882.

[15] Wyngaarden LA, . Oriented cell motility and division underlie early limb bud morphogenesis. Dev. Camb. Engl., 2010, 137: 2551-2558.

[16] Baena-López LA, Baonza A, García-Bellido A. The orientation of cell divisions determines the shape of drosophila organs. Curr. Biol., 2005, 15: 1640-1644.

[17] Wyatt TPJ, . Emergence of homeostatic epithelial packing and stress dissipation through divisions oriented along the long cell axis. Proc. Natl Acad. Sci. USA, 2015, 112: 5726-5731.

[18] Zhou Z, Alégot H, Irvine KD. Oriented cell divisions are not required for drosophila wing shape. Curr. Biol., 2019, 29: 856-864. e3

[19] Campinho P, . Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly. Nat. Cell Biol., 2013, 15: 1405-1414.

[20] Boehm B, . The role of spatially controlled cell proliferation in limb bud morphogenesis. PLoS Biol., 2010, 8

[21] Tao H, . Oscillatory cortical forces promote three dimensional cell intercalations that shape the murine mandibular arch. Nat. Commun., 2019, 10

[22] Footer MJ, Kerssemakers JWJ, Theriot JA, Dogterom M. Direct measurement of force generation by actin filament polymerization using an optical trap. Proc. Natl Acad. Sci. USA, 2007, 104: 2181-2186.

[23] Dogterom M, Yurke B. Measurement of the force-velocity relation for growing microtubules. Science, 1997, 278: 856-860.

[24] Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat. Rev. Mol. Cell Biol., 2009, 10: 778-790.

[25] Munjal A, Lecuit T. Actomyosin networks and tissue morphogenesis. Development, 2014, 141: 1789-1793.

[26] Agarwal P, Zaidel-Bar R. Principles of actomyosin regulation in vivo. Trends Cell Biol., 2019, 29: 150-163.

[27] Martin AC, Kaschube M, Wieschaus EF. Pulsed contractions of an actin-myosin network drive apical constriction. Nature, 2009, 457: 495-499.

[28] Mason FM, Tworoger M, Martin AC. Apical domain polarization localizes actin-myosin activity to drive ratchet-like apical constriction. Nat. Cell Biol., 2013, 15: 926-936.

[29] Borges RM, Lamers ML, Forti FL, Santos MFD, Yan CYI. Rho signaling pathway and apical constriction in the early lens placode. Genes. N. Y. N., 2011, 2000: 368-379.

[30] Sai X, Yonemura S, Ladher RK. Junctionally restricted RhoA activity is necessary for apical constriction during phase 2 inner ear placode invagination. Dev. Biol., 2014, 394: 206-216.

[31] Zhang S, Lee J-M, Ashok AA, Jung H-S. Action of actomyosin contraction with shh modulation drive epithelial folding in the circumvallate papilla. Front. Physiol, 2020, 11: 936.

[32] Kasza KE, Farrell DL, Zallen JA. Spatiotemporal control of epithelial remodeling by regulated myosin phosphorylation. Proc. Natl Acad. Sci. USA, 2014, 111: 11732-11737.

[33] Simões S, . Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation. Dev. Cell, 2010, 19: 377-388.

[34] Rauzi M, Lenne P-F, Lecuit T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature, 2010, 468: 1110-1114.

[35] Bertet C, Sulak L, Lecuit T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature, 2004, 429: 667-671.

[36] Heisenberg CP, . Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature, 2000, 405: 76-81.

[37] Nishimura T, Honda H, Takeichi M. Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell, 2012, 149: 1084-1097.

[38] Keller R. Shaping the vertebrate body plan by polarized embryonic cell movements. Science, 2002, 298: 1950-1954.

[39] Harris TJC, Tepass U. Adherens junctions: from molecules to morphogenesis. Nat. Rev. Mol. Cell Biol., 2010, 11: 502-514.

[40] le Duc Q, . Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J. Cell Biol., 2010, 189: 1107-1115.

[41] Yonemura S, Wada Y, Watanabe T, Nagafuchi A, Shibata M. α-Catenin as a tension transducer that induces adherens junction development. Nat. Cell Biol., 2010, 12: 533-542.

[42] Leerberg JM, . Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens. Curr. Biol. CB, 2014, 24: 1689-1699.

[43] Choi H-J, . αE-catenin is an autoinhibited molecule that coactivates vinculin. Proc. Natl Acad. Sci. USA, 2012, 109: 8576-8581.

[44] Yao M, . Force-dependent conformational switch of α-catenin controls vinculin binding. Nat. Commun., 2014, 5

[45] Shewan AM, . Myosin 2 is a key rho kinase target necessary for the local concentration of E-cadherin at cell–cell contacts. Mol. Biol. Cell, 2005, 16: 4531-4542.

[46] Verma S, . A WAVE2-Arp2/3 actin nucleator apparatus supports junctional tension at the epithelial zonula adherens. Mol. Biol. Cell, 2012, 23: 4601-4610.

[47] Kale GR, . Distinct contributions of tensile and shear stress on E-cadherin levels during morphogenesis. Nat. Commun., 2018, 9: 1-16.

[48] Gittes F, Mickey B, Nettleton J, Howard J. Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape. J. Cell Biol., 1993, 120: 923-934.

[49] Wang N, . Mechanical behavior in living cells consistent with the tensegrity model. Proc. Natl Acad. Sci. USA, 2001, 98: 7765-7770.

[50] Singh A, . Polarized microtubule dynamics directs cell mechanics and coordinates forces during epithelial morphogenesis. Nat. Cell Biol., 2018, 20: 1126-1133.

[51] Takeda M, Sami MM, Wang Y-C. A homeostatic apical microtubule network shortens cells for epithelial folding via a basal polarity shift. Nat. Cell Biol., 2018, 20: 36-45.

[52] Stehbens SJ, . Dynamic microtubules regulate the local concentration of E-cadherin at cell-cell contacts. J. Cell Sci., 2006, 119: 1801-1811.

[53] Sumigray KD, Foote HP, Lechler T. Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation. J. Cell Biol., 2012, 199: 513-525.

[54] Isrie M, . Mutations in either TUBB or MAPRE2 cause circumferential skin creases kunze type. Am. J. Hum. Genet., 2015, 97: 790-800.

[55] Larson TA, Gordon TN, Lau HE, Parichy DM. Defective adult oligodendrocyte and Schwann cell development, pigment pattern, and craniofacial morphology in puma mutant zebrafish having an alpha tubulin mutation. Dev. Biol., 2010, 346: 296-309.

[56] Joo EE, Yamada KM. MYPT1 regulates contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly. Nat. Commun., 2014, 5

[57] Short KM, Hopwood B, Yi Z, Cox TC. MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, Alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders. BMC Cell Biol., 2002, 3

[58] Shwartz Y, Blitz E, Zelzer E. One load to rule them all: mechanical control of the musculoskeletal system in development and aging. Differentiation, 2013, 86: 104-111.

[59] Hall BK, Herring SW. Paralysis and growth of the musculoskeletal system in the embryonic chick. J. Morphol., 1990, 206: 45-56.

[60] Hogg DA, Hosseini A. The effects of paralysis on skeletal development in the chick embryo. Comp. Biochem. Physiol. A Physiol., 1992, 103: 25-28.

[61] Sharir A, Stern T, Rot C, Shahar R, Zelzer E. Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis. Development, 2011, 138: 3247-3259.

[62] Pai AC. Developmental genetics of a lethal mutation, muscular dysgenesis (mdg), in the mouse: I. Genetic analysis and gross morphology. Dev. Biol., 1965, 11: 82-92.

[63] Rot-Nikcevic I, . Myf5−/−:MyoD−/−amyogenic fetuses reveal the importance of early contraction and static loading by striated muscle in mouse skeletogenesis. Dev. Genes Evol., 2006, 216: 1-9.

[64] Blitz E, . Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Dev. Cell, 2009, 17: 861-873.

[65] Maeda T, . Conversion of mechanical force into TGF-β-mediated biochemical signals. Curr. Biol., 2011, 21: 933-941.

[66] Huang AH, . Musculoskeletal integration at the wrist underlies the modular development of limb tendons. Dev. Camb. Engl., 2015, 142: 2431-2441.

[67] Kahn J, . Muscle contraction is necessary to maintain joint progenitor cell fate. Dev. Cell, 2009, 16: 734-743.

[68] Solem RC, Eames BF, Tokita M, Schneider RA. Mesenchymal and mechanical mechanisms of secondary cartilage induction. Dev. Biol., 2011, 356: 28-39.

[69] Shwartz Y, Farkas Z, Stern T, Aszódi A, Zelzer E. Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension. Dev. Biol., 2012, 370: 154-163.

[70] Subramanian A, Kanzaki LF, Galloway JL, Schilling TF. Mechanical force regulates tendon extracellular matrix organization and tenocyte morphogenesis through TGFbeta signaling. eLife, 2018, 7: e38069.

[71] Jones DC, Zelditch ML, Peake PL, German RZ. The effects of muscular dystrophy on the craniofacial shape of Mus musculus. J. Anat., 2007, 210: 723-730.

[72] Lightfoot PS, German RZ. The effects of muscular dystrophy on craniofacial growth in mice: a study of heterochrony and ontogenetic allometry. J. Morphol., 1998, 235: 1-16.

[73] Matsuyuki T, Kitahara T, Nakashima A. Developmental changes in craniofacial morphology in subjects with Duchenne muscular dystrophy. Eur. J. Orthod., 2006, 28: 42-50.

[74] Wong M, Siegrist M, Goodwin K. Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes. Bone, 2003, 33: 685-693.

[75] Mikic B, Isenstein AL, Chhabra A. Mechanical modulation of cartilage structure and function during embryogenesis in the chick. Ann. Biomed. Eng., 2004, 32: 18-25.

[76] Luu O, David R, Ninomiya H, Winklbauer R. Large-scale mechanical properties of Xenopus embryonic epithelium. Proc. Natl Acad. Sci.USA, 2011, 108: 4000-4005.

[77] Zhou J, Kim HY, Davidson LA. Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and neural tube closure. Dev. Camb. Engl., 2009, 136: 677-688.

[78] Shawky JH, Balakrishnan UL, Stuckenholz C, Davidson LA. Multiscale analysis of architecture, cell size and the cell cortex reveals cortical F-actin density and composition are major contributors to mechanical properties during convergent extension. Development, 2018, 145: 161281.

[79] Iyer KV, Piscitello-Gómez R, Paijmans J, Jülicher F, Eaton S. Epithelial viscoelasticity is regulated by mechanosensitive E-cadherin turnover. Curr. Biol. CB, 2019, 29: 578-591 e5..

[80] Serwane F, . In vivo quantification of spatially varying mechanical properties in developing tissues. Nat. Methods, 2017, 14: 181-186.

[81] Mongera A, . A fluid-to-solid jamming transition underlies vertebrate body axis elongation. Nature, 2018, 561: 401.

[82] Bénazéraf B, . A random cell motility gradient downstream of FGF controls elongation of an amniote embryo. Nature, 2010, 466: 248-252.

[83] Dzamba, B. J. & DeSimone, D. W. Extracellular matrix (ECM) and the sculpting of embryonic tissues. In Current Topics in Developmental Biology (eds. Litscher, E. S. & Wassarman, P. M.) Vol. 130, 245–274 (Academic Press, 2018).

[84] del Rio A, . Stretching single talin rod molecules activates vinculin binding. Science, 2009, 323: 638-641.

[85] Yao M, . Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. Sci. Rep., 2014, 4

[86] Muncie, J. M. & Weaver, V. M. The physical and biochemical properties of the extracellular matrix regulate cell fate. In Current Topics in Developmental Biology (eds. Litscher, E. S. & Wassarman, P. M.) Vol. 130, 1–37 (Academic Press, 2018).

[87] Nakanishi Y, Sugiura F, Kishi J, Hayakawa T. Collagenase inhibitor stimulates cleft formation during early morphogenesis of mouse salivary gland. Dev. Biol., 1986, 113: 201-206.

[88] Sakai T, Larsen M, Yamada KM. Fibronectin requirement in branching morphogenesis. Nature, 2003, 423: 876-881.

[89] Daley WP, Gulfo KM, Sequeira SJ, Larsen M. Identification of a mechanochemical checkpoint and negative feedback loop regulating branching morphogenesis. Dev. Biol., 2009, 336: 169-182.

[90] Daley WP, Kohn JM, Larsen M. A focal adhesion protein-based mechanochemical checkpoint regulates cleft progression during branching morphogenesis. Dev. Dyn., 2011, 240: 2069-2083.

[91] Barriga EH, Franze K, Charras G, Mayor R. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo. Nature, 2018, 554: 523-527.

[92] Thesleff I, Vainio S, Jalkanen M. Cell-matrix interactions in tooth development. Int. J. Dev. Biol., 1989, 33: 91-97.

[93] Mammoto Tadanori, . Mesenchymal condensation‐dependent accumulation of collagen VI stabilizes organ‐specific cell fates during embryonic tooth formation. Dev. Dyn., 2015, 244: 713-723.

[94] Huang J, . The mechanism of lens placode formation: a case of matrix-mediated morphogenesis. Dev. Biol., 2011, 355: 32-42.

[95] Bogdanović O, . Numb/Numbl-Opo antagonism controls retinal epithelium morphogenesis by regulating integrin endocytosis. Dev. Cell, 2012, 23: 782-795.

[96] Visconti RP, Hilfer SR. Perturbation of extracellular matrix prevents association of the otic primordium with the posterior rhombencephalon and inhibits subsequent invagination. Dev. Dyn., 2002, 223: 48-58.

[97] Geng F-S, . Semicircular canal morphogenesis in the zebrafish inner ear requires the function of gpr126 (lauscher), an adhesion class G protein-coupled receptor gene. Development, 2013, 140: 4362-4374.

[98] Croucher SJ, Tickle C. Characterization of epithelial domains in the nasal passages of chick embryos: spatial and temporal mapping of a range of extracellular matrix and cell surface molecules during development of the nasal placode. Dev. Camb. Engl., 1989, 106: 493-509.

[99] Karaman R, Halder G. Cell junctions in Hippo signaling. Cold Spring Harb. Perspect. Biol., 2018, 10: a028753.

[100] Schlegelmilch K, . Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell, 2011, 144: 782-795.

[101] Zhao B, . Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev., 2011, 25: 51-63.

[102] Feng X, . A platform of synthetic lethal gene interaction networks reveals that the GNAQ uveal melanoma oncogene controls the Hippo pathway through FAK. Cancer Cell, 2019, 35: 457-472. e5

[103] Li P, . αE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway. Genes Dev., 2016, 30: 798-811.

[104] Dupont S, . Role of YAP/TAZ in mechanotransduction. Nature, 2011, 474: 179-183.

[105] Elosegui-Artola A, . Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat. Cell Biol., 2016, 18: 540-548.

[106] Kim N-G, Gumbiner BM. Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway. J. Cell Biol., 2015, 210: 503-515.

[107] Elosegui-Artola A, . Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell, 2017, 171: 1397-1410. e14

[108] Rauskolb C, Sun S, Sun G, Pan Y, Irvine KD. Cytoskeletal tension inhibits Hippo signaling through an Ajuba-Warts complex. Cell, 2014, 158: 143-156.

[109] Ibar C, . Tension-dependent regulation of mammalian Hippo signaling through LIMD1. J. Cell Sci., 2018, 131: jcs214700.

[110] Wang J, . Yap and Taz play a crucial role in neural crest-derived craniofacial development. Development, 2016, 143: 504-515.

[111] Liu M, Zhao S, Lin Q, Wang X-P. YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues. Mol. Cell. Biol., 2015, 35: 1449-1461.

[112] Goodwin, A. F., Chen, C. P., Vo, N. T., Bush, J. O. & Klein, O. D. YAP/TAZ regulate elevation and bone formation of the mouse secondary palate. J. Dent. Res. 0022034520935372 https://doi.org/10.1177/0022034520935372. (2020)

[113] McMillin MJ, . Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. Am. J. Hum. Genet., 2014, 94: 734-744.

[114] Wu J, Lewis AH, Grandl J. Touch, tension, and transduction–the function and regulation of piezo ion channels. Trends Biochem. Sci., 2017, 42: 57-71.

[115] Eisenhoffer GT, . Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature, 2012, 484: 546-549.

[116] Pathak MM, . Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. Proc. Natl Acad. Sci. USA, 2014, 111: 16148-16153.

[117] He L, Si G, Huang J, Samuel ADT, Perrimon N. Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel. Nature, 2018, 555: 103-106.

[118] Okubo T, . Ripply3, a Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice. Development, 2011, 138: 339-348.

[119] Frisdal A, Trainor PA. Development and evolution of the pharyngeal apparatus. Wiley Interdiscip. Rev. Dev. Biol., 2014, 3: 403-418.

[120] Wilkie AOM, Morriss-Kay GM. Genetics of craniofacial development and malformation. Nat. Rev. Genet., 2001, 2: 458-468.

[121] Trumpp A, Depew MJ, Rubenstein JL, Bishop JM, Martin GR. Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev., 1999, 13: 3136-3148.

[122] Berge Dten, . Prx1 and Prx2 are upstream regulators of sonic hedgehog and control cell proliferation during mandibular arch morphogenesis. Development, 2001, 128: 2929-2938.

[123] Ota MS, . Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells. Dev. Dyn., 2004, 230: 216-228.

[124] Yamaguchi TP, Bradley A, McMahon AP, Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development, 1999, 126: 1211-1223.

[125] Person AD, . WNT5A mutations in patients with autosomal dominant Robinow syndrome. Dev. Dyn., 2010, 239: 327-337.

[126] Gros J, . WNT5A/JNK and FGF/MAPK pathways regulate the cellular events shaping the vertebrate limb bud. Curr. Biol., 2010, 20: 1993-2002.

[127] Hosseini-Farahabadi, S., Gignac, S. J., Danescu, A., Fu, K. & Richman, J. M. Abnormal WNT5A signaling causes mandibular hypoplasia in Robinow syndrome. J. Dent. Res. https://doi.org/10.1177/0022034517716916. (2017).

[128] Zhu M, Zhang K, Tao H, Hopyan S, Sun Y. Magnetic micromanipulation for in vivo measurement of stiffness heterogeneity and anisotropy in the mouse mandibular arch. Research, 2020, 2020: 7914074.

[129] Smith MM. Vertebrate dentitions at the origin of jaws: when and how pattern evolved. Evol. Dev., 2003, 5: 394-413.

[130] Thesleff I, Nieminen P. Tooth morphogenesis and cell differentiation. Curr. Opin. Cell Biol., 1996, 8: 844-850.

[131] Yu T, Klein OD. Molecular and cellular mechanisms of tooth development, homeostasis and repair. Development, 2020, 147: dev184754.

[132] Kim R, Green JBA, Klein OD. From snapshots to movies: understanding early tooth development in four dimensions. Dev. Dyn., 2017, 246: 442-450.

[133] Panousopoulou E, Green JBA. Invagination of ectodermal placodes is driven by cell intercalation-mediated contraction of the suprabasal tissue canopy. PLoS Biol., 2016, 14: e1002405.

[134] Pearl EJ, Li J, Green JBA. Cellular systems for epithelial invagination. Philos. Trans. R. Soc. Lond. B, 2017, 372: 20150526.

[135] Li J, Economou AD, Vacca B, Green JBA. Epithelial invagination by a vertical telescoping cell movement in mammalian salivary glands and teeth. Nat. Commun., 2020, 11

[136] Li J, Chatzeli L, Panousopoulou E, Tucker AS, Green JBA. Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth. Dev. Camb. Engl., 2016, 143: 670-681.

[137] Mammoto T, . Mechanochemical control of mesenchymal condensation and embryonic tooth organ formation. Dev. Cell, 2011, 21: 758-769.

[138] Butler PM. Distribution of mitoses in the inner enamel epithelium of molar tooth germs of the mouse. J. Dent. Res., 1962, 41: 1261-1262.

[139] Jernvall J, Aberg T, Kettunen P, Keränen S, Thesleff I. The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot. Dev. Camb. Engl., 1998, 125: 161-169.

[140] Vaahtokari A, Åberg T, Jernvall J, Keränen S, Thesleff I. The enamel knot as a signaling center in the developing mouse tooth. Mech. Dev., 1996, 54: 39-43.

[141] Salazar-Ciudad I, Jernvall J. A computational model of teeth and the developmental origins of morphological variation. Nature, 2010, 464: 583-586.

[142] Morita R, . Coordination of cellular dynamics contributes to tooth epithelium deformations. PLoS ONE, 2016, 11

[143] Takigawa-Imamura H, Morita R, Iwaki T, Tsuji T, Yoshikawa K. Tooth germ invagination from cell-cell interaction: Working hypothesis on mechanical instability. J. Theor. Biol., 2015, 382: 284-291.

[144] Marin-Riera M, Moustakas-Verho J, Savriama Y, Jernvall J, Salazar-Ciudad I. Differential tissue growth and cell adhesion alone drive early tooth morphogenesis: an ex vivo and in silico study. PLoS Comput. Biol., 2018, 14

[145] Yamada S, Lav R, Li J, Tucker AS, Green JBA. Molar bud-to-cap transition is proliferation independent. J. Dent. Res., 2019, 98: 1253-1261.

[146] Li C-Y, . E-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development. Nat. Commun., 2016, 7

[147] Jernvall, J., Keränen, S. V. E. & Thesleff, I. Evolutionary modification of development in mammalian teeth: quantifying gene expression patterns and topography. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.97.26.14444. (2000).

[148] Coin R, Lesot H, Vonesch JL, Haikel Y, Ruch JV. Aspects of cell proliferation kinetics of the inner dental epithelium during mouse molar and incisor morphogenesis: a reappraisal of the role of the enamel knot area. Int. J. Dev. Biol., 1999, 43: 261-267.

[149] Du W, Hu JK-H, Du W, Klein OD. Lineage tracing of epithelial cells in developing teeth reveals two strategies for building signaling centers. J. Biol. Chem., 2017, 292: 15062-15069.

[150] Jernvall J, Thesleff I. Tooth shape formation and tooth renewal: evolving with the same signals. Development, 2012, 139: 3487-3497.

[151] Renvoisé E, . Mechanical constraint from growing jaw facilitates mammalian dental diversity. Proc. Natl Acad. Sci. USA, 2017, 114: 9403-9408.

[152] Wu X, . Biomechanical stress regulates mammalian tooth replacement via the integrin β1-RUNX2-Wnt pathway. EMBO J., 2020, 39

[153] Smith EE, . Developing a biomimetic tooth bud model. J. Tissue Eng. Regen. Med., 2017, 11: 3326.

[154] Brown TE, Anseth KS. Spatiotemporal hydrogel biomaterials for regenerative medicine. Chem. Soc. Rev., 2017, 46: 6532-6552.

[155] Krueger D, . Principles and applications of optogenetics in developmental biology. Development, 2019, 146: dev175067.

[156] Marrelli M, . Dental pulp stem cell mechanoresponsiveness: effects of mechanical stimuli on dental pulp stem cell behavior. Front. Physiol., 2018, 9: 1685.

[157] Zhang R, Wan J, Wang H. Mechanical strain triggers differentiation of dental mesenchymal stem cells by activating osteogenesis-specific biomarkers expression. Am. J. Transl. Res., 2019, 11: 233-244.

[158] Ito Y, . Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects. Development, 2003, 130: 5269-5280.

[159] Bush JO, Jiang R. Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development. Development, 2012, 139: 231-243.

[160] Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat. Rev. Genet., 2011, 12: 167-178.

[161] Kaartinen V, . Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Nat. Genet., 1995, 11: 415-421.

[162] Ingraham CR, . Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat. Genet., 2006, 38: 1335-1340.

[163] Richardson RJ, . Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat. Genet., 2006, 38: 1329-1334.

[164] Ke C-Y, Xiao W-L, Chen C-M, Lo L-J, Wong F-H. IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion. Sci. Rep., 2015, 5

[165] Vieira AR. Unraveling human cleft lip and palate research. J. Dent. Res., 2008, 87: 119-125.

[166] Kondo S, . Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat. Genet., 2002, 32: 285-289.

[167] Jin J-Z, . Mesenchymal cell remodeling during mouse secondary palate reorientation. Dev. Dyn., 2010, 239: 2110-2117.

[168] Yu K, Ornitz DM. Histomorphological study of palatal shelf elevation during murine secondary palate formation. Dev. Dyn., 2011, 240: 1737-1744.

[169] Brock LJ, Economou AD, Cobourne MT, Green JBA. Mapping cellular processes in the mesenchyme during palatal development in the absence of Tbx1 reveals complex proliferation changes and perturbed cell packing and polarity. J. Anat., 2016, 228: 464-473.

[170] Lan Y, . Odd-skipped related 2 (Osr2) encodes a key intrinsic regulator of secondary palate growth and morphogenesis. Development, 2004, 131: 3207-3216.

[171] Chiquet M, Blumer S, Angelini M, Mitsiadis TA, Katsaros C. Mesenchymal remodeling during palatal shelf elevation revealed by extracellular matrix and F-actin expression patterns. Front. Physiol., 2016, 7: 392.

[172] Wang X, . Extracellular matrix remodeling during palate development. Organogenesis, 2020, 16: 43-60.

[173] Wang C, . Type 1 fibroblast growth factor receptor in cranial neural crest cell-derived mesenchyme is required for palatogenesis. J. Biol. Chem., 2013, 288: 22174-22183.

[174] Pratt RM, Goggins JF, Wilk AL, King CT. Acid mucopolysaccharide synthesis in the secondary palate of the developing rat at the time of rotation and fusion. Dev. Biol., 1973, 32: 230-237.

[175] Ferguson MW. Palate development. Dev. Camb. Engl., 1988, 103: 41-60.

[176] Galloway JL, Jones SJ, Mossey PA, Ellis IR. The control and importance of hyaluronan synthase expression in palatogenesis. Front. Physiol., 2013, 4: 10.

[177] Lan Y, Qin C, Jiang R. Requirement of hyaluronan synthase-2 in craniofacial and palate development. J. Dent. Res., 2019, 98: 1367-1375.

[178] Yonemitsu MA, Lin T, Yu K. Hyaluronic acid is required for palatal shelf movement and its interaction with the tongue during palatal shelf elevation. Dev. Biol., 2020, 457: 57-68.

[179] Yu K, Yonemitsu MA. In vitro analysis of palatal shelf elevation during secondary palate formation. Anat. Rec. Hoboken NJ, 2019, 2007: 1594-1604.

[180] Zhang J, . Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice. Hum. Mol. Genet., 2015, 24: 6174-6185.

[181] Vanyai, H. K. et al. Control of skeletal morphogenesis by the Hippo-YAP/TAZ pathway. Development https://doi.org/10.1242/dev.187187. (2020).

[182] Fitchett JE, Hay ED. Medial edge epithelium transforms to mesenchyme after embryonic palatal shelves fuse. Dev. Biol., 1989, 131: 455-474.

[183] Griffith CM, Hay ED. Epithelial-mesenchymal transformation during palatal fusion: carboxyfluorescein traces cells at light and electron microscopic levels. Dev. Camb. Engl., 1992, 116: 1087-1099.

[184] Shuler CF, Guo Y, Majumder A, Luo RY. Molecular and morphologic changes during the epithelial-mesenchymal transformation of palatal shelf medial edge epithelium in vitro. Int. J. Dev. Biol., 1991, 35: 463-472.

[185] Martínez-Alvarez C, . Medial edge epithelial cell fate during palatal fusion. Dev. Biol., 2000, 220: 343-357.

[186] DeAngelis V, Nalbandian J. Ultrastructure of mouse and rat palatal processes prior to and during secondary palate formation. Arch. Oral. Biol., 1968, 13: 601-IN7.

[187] Cuervo R, Valencia C, Chandraratna RAS, Covarrubias L. Programmed cell death is required for palate shelf fusion and is regulated by retinoic acid. Dev. Biol., 2002, 245: 145-156.

[188] Cuervo R, Covarrubias L. Death is the major fate of medial edge epithelial cells and the cause of basal lamina degradation during palatogenesis. Development, 2004, 131: 15-24.

[189] Carette MJ, Ferguson MW. The fate of medial edge epithelial cells during palatal fusion in vitro: an analysis by DiI labelling and confocal microscopy. Dev. Camb. Engl., 1992, 114: 379-388.

[190] Jin J-Z, Ding J. Analysis of cell migration, transdifferentiation and apoptosis during mouse secondary palate fusion. Development, 2006, 133: 3341-3347.

[191] Lohnes D, . Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. Dev. Camb. Engl., 1994, 120: 2723-2748.

[192] Richardson RJ, Dixon J, Jiang R, Dixon MJ. Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence. Hum. Mol. Genet., 2009, 18: 2632-2642.

[193] Iwata J, . Smad4-Irf6 genetic interaction and TGFβ-mediated IRF6 signaling cascade are crucial for palatal fusion in mice. Dev. Camb. Engl., 2013, 140: 1220-1230.

[194] Lane J, . Tak1, Smad4 and Trim33 redundantly mediate TGF-β3 signaling during palate development. Dev. Biol., 2015, 398: 231-241.

[195] Ke FFS, . Embryogenesis and adult life in the absence of intrinsic apoptosis effectors BAX, BAK, and BOK. Cell, 2018, 173: 1217-1230. e17

[196] Kim S, . Convergence and extrusion are required for normal fusion of the mammalian secondary palate. PLoS Biol., 2015, 13

[197] Li, J. et al. Linking suckling biomechanics to the development of the palate. Sci. Rep. 6, (2016).

[198] Yuan Y, Chai Y. Regulatory mechanisms of jaw bone and tooth development. Curr. Top. Dev. Biol., 2019, 133: 91-118.

[199] Ivkovic S, . Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development, 2003, 130: 2779-2791.

[200] Mori-Akiyama Y, Akiyama H, Rowitch DH, de Crombrugghe B. Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Proc. Natl Acad. Sci. USA, 2003, 100: 9360-9365.

[201] Wolff, J. The Law of Bone Remodelling (Translation of the original German edition). (Springer-Verlag, 1892).

[202] Habib H, Hatta T, Rahman OIF, Yoshimura Y, Otani H. Fetal jaw movement affects development of articular disk in the temporomandibular joint. Congenit. Anom., 2007, 47: 53-57.

[203] Habib H, . Fetal jaw movement affects condylar cartilage development. J. Dent. Res., 2005, 84: 474-479.

[204] Jahan E, . Fetal jaw movement affects Ihh signaling in mandibular condylar cartilage development: the possible role of Ihh as mechanotransduction mediator. Arch. Oral. Biol., 2014, 59: 1108-1118.

[205] Wu Q, Zhang Y, Chen Q. Indian hedgehog is an essential component of mechanotransduction complex to stimulate chondrocyte proliferation. J. Biol. Chem., 2001, 276: 35290-35296.

[206] Brunt LH, Norton JL, Bright JA, Rayfield EJ, Hammond CL. Finite element modelling predicts changes in joint shape and cell behaviour due to loss of muscle strain in jaw development. J. Biomech., 2015, 48: 3112-3122.

[207] Brunt LH, . Differential effects of altered patterns of movement and strain on joint cell behaviour and skeletal morphogenesis. Osteoarthr. Cartil., 2016, 24: 1940-1950.

[208] Brunt LH, Begg K, Kague E, Cross S, Hammond CL. Wnt signalling controls the response to mechanical loading during zebrafish joint development. Development, 2017, 144: 2798-2809.

[209] Sella-Tunis T, Pokhojaev A, Sarig R, O’Higgins P, May H. Human mandibular shape is associated with masticatory muscle force. Sci. Rep., 2018, 8

[210] Kiliaridis S, Mejersjö C, Thilander B. Muscle function and craniofacial morphology: a clinical study in patients with myotonic dystrophy. Eur. J. Orthod., 1989, 11: 131-138.

[211] Hassan MG, . Effects of multi-generational soft diet consumption on mouse craniofacial morphology. Front. Physiol, 2020, 11: 783.

[212] Simon MR. The role of compressive forces in the normal maturation of the condylar cartilage in the rat. Cells Tissues Organs, 1977, 97: 351-360.

[213] Hinton RJ, Carlson DS. Response of the MAndibular Joint to Loss of Incisal Function in the Rat. Cells Tissues Organs, 1986, 125: 145-151.

[214] Kantomaa T, Tuominen M, Pirttiniemi P. Effect of mechanical forces on chondrocyte maturation and differentiation in the mandibular condyle of the rat. J. Dent. Res., 1994, 73: 1150-1156.

[215] Sasaguri K, Jiang H, Chen J. The effect of altered functional forces on the expression of bone-matrix proteins in developing mouse mandibular condyle. Arch. Oral. Biol., 1998, 43: 83-92.

[216] Pirttiniemi P, Kantomaa T, Sorsa T. Effect of decreased loading on the metabolic activity of the mandibular condylar cartilage in the rat. Eur. J. Orthod., 2004, 26: 1-5.

[217] Wang X, Mao JJ. Chondrocyte proliferation of the cranial base cartilage upon in vivo mechanical stresses. J. Dent. Res., 2002, 81: 701-705.

[218] Sobue T, . Murine TMJ loading causes increased proliferation and chondrocyte maturation. J. Dent. Res., 2011, 90: 512-516.

[219] Tang GH, Rabie ABM, Hägg U. Indian Hedgehog: a mechanotransduction mediator in condylar cartilage. J. Dent. Res., 2004, 83: 434-438.

[220] Shao YY, Wang L, Welter JF, Ballock RT. Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes. Bone, 2012, 50: 79-84.

[221] Kinumatsu T, . TMJ development and growth require primary cilia function. J. Dent. Res., 2011, 90: 988-994.

[222] Woronowicz KC, Gline SE, Herfat ST, Fields AJ, Schneider RA. FGF and TGFβ signaling link form and function during jaw development and evolution. Dev. Biol., 2018, 444: S219-S236.

[223] Sprinz R. A note on the mandibular intra-articular disc in the joints of marsupialia and monotremata. Proc. Zool. Soc. Lond., 1965, 144: 327-337.

[224] El Adli JJ, Deméré TA. On the anatomy of the temporomandibular joint and the muscles that act upon it: observations on the gray whale, Eschrichtius robustus. Anat. Rec. Hoboken NJ, 2015, 2007: 680-690.

[225] Anthwal N, Tucker AS. The TMJ disc is a common ancestral feature in all mammals, as evidenced by the presence of a rudimentary disc during monotreme development. Front. Cell Dev. Biol., 2020, 8: 356.

[226] Marcucio RS, Young NM, Hu D, Hallgrimsson B. Mechanisms that underlie co-variation of the brain and face. Genesis, 2011, 49: 177-189.

[227] Ishii M, Sun J, Ting M-C, Maxson RE. The development of the calvarial bones and sutures and the pathophysiology of craniosynostosis. Curr. Top. Dev. Biol., 2015, 115: 131-156.

[228] Jiang X, Iseki S, Maxson RE, Sucov HM, Morriss-Kay GM. Tissue origins and interactions in the mammalian skull vault. Dev. Biol., 2002, 241: 106-116.

[229] Yoshida T, Vivatbutsiri P, Morriss-Kay G, Saga Y, Iseki S. Cell lineage in mammalian craniofacial mesenchyme. Mech. Dev., 2008, 125: 797-808.

[230] Ting M-C, . EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Development, 2009, 136: 855-864.

[231] Deckelbaum RA, . Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1. Development, 2012, 139: 1346-1358.

[232] Opperman LA. Cranial sutures as intramembranous bone growth sites. Dev. Dyn., 2000, 219: 472-485.

[233] Lana-Elola E, Rice R, Grigoriadis AE, Rice DPC. Cell fate specification during calvarial bone and suture development. Dev. Biol., 2007, 311: 335-346.

[234] Zhao H, . The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat. Cell Biol., 2015, 17: 386-396.

[235] Maruyama T, Jeong J, Sheu T-J, Hsu W. Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration. Nat. Commun., 2016, 7

[236] Wilk K, . Postnatal calvarial skeletal stem cells expressing PRX1 reside exclusively in the calvarial sutures and are required for bone regeneration. Stem Cell Rep., 2017, 8: 933-946.

[237] Wu X, Gu Y. Signaling mechanisms underlying genetic pathophysiology of craniosynostosis. Int. J. Biol. Sci., 2019, 15: 298-311.

[238] Agochukwu NB, Solomon BD, Muenke M. Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses. Childs Nerv. Syst., 2012, 28: 1447-1463.

[239] Felsenthal N, Zelzer E. Mechanical regulation of musculoskeletal system development. Dev. Camb. Engl., 2017, 144: 4271-4283.

[240] Opperman LA, Sweeney TM, Redmon J, Persing JA, Ogle RC. Tissue interactions with underlying dura mater inhibit osseous obliteration of developing cranial sutures. Dev. Dyn., 1993, 198: 312-322.

[241] Mabbutt LW, Kokich VG. Calvarial and sutural re-development following craniectomy in the neonatal rabbit. J. Anat., 1979, 129: 413-422.

[242] Moss ML, Young RW. A functional approach to craniology. Am. J. Phys. Anthropol., 1960, 18: 281-292.

[243] Moazen M, . Intracranial pressure changes during mouse development. J. Biomech., 2016, 49: 123-126.

[244] Henderson JH, Chang LY, Song HM, Longaker MT, Carter DR. Age-dependent properties and quasi-static strain in the rat sagittal suture. J. Biomech., 2005, 38: 2294-2301.

[245] Henderson JH, Nacamuli RP, Zhao B, Longaker MT, Carter DR. Age-dependent residual tensile strains are present in the dura mater of rats. J. R. Soc. Interface, 2005, 2: 159-167.

[246] Albright AL, Tyler-Kabara E. Slit-ventricle syndrome secondary to shunt-induced suture ossification. Neurosurgery, 2001, 48: 764-769. discussion 769-770

[247] Cohen MM. Sutural biology and the correlates of craniosynostosis. Am. J. Med. Genet., 1993, 47: 581-616.

[248] Hickory WB, Nanda R. Effect of tensile force magnitude on release of cranial suture cells into S phase. Am. J. Orthod. Dentofac. Orthop., 1987, 91: 328-334.

[249] Miyawaki S, Forbes DP. The morphologic and biochemical effects of tensile force application to the interparietal suture of the Sprague-Dawley rat. Am. J. Orthod. Dentofac. Orthop., 1987, 92: 123-133.

[250] Ikegame M, . Tensile stress induces bone morphogenetic protein 4 in preosteoblastic and fibroblastic cells, which later differentiate into osteoblasts leading to osteogenesis in the mouse calvariae in organ culture. J. Bone Miner. Res., 2001, 16: 24-32.

[251] Hirukawa K, . Effect of tensile force on the expression of IGF-I and IGF-I receptor in the organ-cultured rat cranial suture. Arch. Oral. Biol., 2005, 50: 367-372.

[252] Ogle RC, Tholpady SS, McGlynn KA, Ogle RA. Regulation of cranial suture morphogenesis. Cells Tissues Organs, 2004, 176: 54-66.

[253] Yu JC, Lucas JH, Fryberg K, Borke JL. Extrinsic tension results in FGF-2 release, membrane permeability change, and intracellular Ca++ increase in immature cranial sutures. J. Craniofac. Surg., 2001, 12: 391-398.

[254] Borke JL, . Tension-induced reduction in connexin 43 expression in cranial sutures is linked to transcriptional regulation by TBX2. Ann. Plast. Surg., 2003, 51: 499-504.

[255] Lin F-X, . Connexin 43 modulates osteogenic differentiation of bone marrow stromal cells through GSK-3beta/Beta-Catenin signaling pathways. Cell. Physiol. Biochem., 2018, 47: 161-175.

[256] Morinobu M, . Osteopontin expression in osteoblasts and osteocytes during bone formation under mechanical stress in the calvarial suture in vivo. J. Bone Miner. Res., 2003, 18: 1706-1715.

[257] Ikegame M, Ejiri S, Okamura H. Expression of non-collagenous bone matrix proteins in osteoblasts stimulated by mechanical stretching in the cranial suture of neonatal mice. J. Histochem. Cytochem., 2019, 67: 107-116.

[258] Shimomura J, . Tensile stress induces α-adaptin C production in mouse calvariae in an organ culture: Possible involvement of endocytosis in mechanical stress-stimulated osteoblast differentiation. J. Cell. Physiol., 2003, 195: 488-496.

[259] Choi YH, Choi J-H, Oh J-W, Lee K-Y. Calmodulin-dependent kinase II regulates osteoblast differentiation through regulation of Osterix. Biochem. Biophys. Res. Commun., 2013, 432: 248-255.

[260] Zayzafoon M, Fulzele K, McDonald JM. Calmodulin and calmodulin-dependent kinase IIα regulate osteoblast differentiation by controlling c-fos expression. J. Biol. Chem., 2005, 280: 7049-7059.

[261] Sun W, . The mechanosensitive Piezo1 channel is required for bone formation. ELife, 2019, 8: e47454.

[262] Persson M. The role of movements in the development of sutural and diarthrodial joints tested by long-term paralysis of chick embryos. J. Anat., 1983, 137: 591-599.

[263] Moss ML. Extrinsic determination of sutural area morphology in the rat calvaria. Acta Anat., 1961, 44: 263-272.

[264] Engström C, Kiliaridis S, Thilander B. The relationship between masticatory function and craniofacial morphology. II. A histological study in the growing rat fed a soft diet. Eur. J. Orthod., 1986, 8: 271-279.

[265] Kaku M, . Remodeling of the sagittal suture in osteopetrotic (op/op) mice associated with cranial flat bone growth. J. Craniofac. Genet. Dev. Biol., 1999, 19: 109-112.

[266] Byron CD, . Effects of increased muscle mass on mouse sagittal suture morphology and mechanics. Anat. Rec. A. Discov. Mol. Cell. Evol. Biol., 2004, 279A: 676-684.

[267] Vecchione L, . Craniofacial morphology in myostatin-deficient mice. J. Dent. Res., 2007, 86: 1068-1072.

[268] Vecchione L, . Age related changes in craniofacial morphology in GDF-8 (Myostatin) deficient mice. Anat. Rec. Hoboken NJ, 2010, 2007: 32-41.

[269] Kopher RA, Mao JJ. Suture growth modulated by the oscillatory component of micromechanical strain. J. Bone Miner. Res., 2003, 18: 521-528.

[270] Al-Mubarak R, Da Silveira A, Mao JJ. Expression and mechanical modulation of matrix metalloproteinase-1 and -2 genes in facial and cranial sutures. Cell Tissue Res., 2005, 321: 465-471.

[271] Collins JM, Ramamoorthy K, Silveira AD, Patston P, Mao JJ. Expression of matrix metalloproteinase genes in the rat intramembranous bone during postnatal growth and upon mechanical stresses. J. Biomech., 2005, 38: 485-492.

[272] Vij K, Mao JJ. Geometry and cell density of rat craniofacial sutures during early postnatal development and upon in vivo cyclic loading. Bone, 2006, 38: 722-730.

[273] Peptan AI, Lopez A, Kopher RA, Mao JJ. Responses of intramembranous bone and sutures upon in vivo cyclic tensile and compressive loading. Bone, 2008, 42: 432-438.

[274] Soh SH, Rafferty K, Herring S. Cyclic loading effects on craniofacial strain and sutural growth in pigs. Am. J. Orthod. Dentofac. Orthop., 2018, 154: 270-282.

[275] Mosig RA, . Loss of MMP-2 disrupts skeletal and craniofacial development, and results in decreased bone mineralization, joint erosion, and defects in osteoblast and osteoclast growth. Hum. Mol. Genet., 2007, 16: 1113-1123.

[276] Li W, . ROCK-TAZ signaling axis regulates mechanical tension-induced osteogenic differentiation of rat cranial sagittal suture mesenchymal stem cells. J. Cell. Physiol., 2020, 235: 5972-5984.

[277] Barreto S, González-Vázquez A, R. Cameron A, O’Brien FJ, Murray DJ. Identification of stiffness-induced signalling mechanisms in cells from patent and fused sutures associated with craniosynostosis. Sci. Rep., 2017, 7

[278] Cho S, Irianto J, Discher DE. Mechanosensing by the nucleus: from pathways to scaling relationships. J. Cell Biol., 2017, 216: 305-315.

[279] Somech R, Shaklai S, Amariglio N, Rechavi G, Simon AJ. Nuclear envelopathies—raising the nuclear veil. Pediatr. Res., 2005, 57: 8-15.

[280] de Carlos F, . Microcephalia with mandibular and dental dysplasia in adult Zmpste24-deficient mice. J. Anat., 2008, 213: 509-519.

[281] Campàs O, . Quantifying cell-generated mechanical forces within living embryonic tissues. Nat. Methods, 2014, 11: 183-189.

[282] Zhu M, . Spatial mapping of tissue properties in vivo reveals a 3D stiffness gradient in the mouse limb bud. Proc. Natl Acad. Sci. USA, 2020, 117: 4781-4791.

Funding

U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)(R00DE025874)

National Natural Science Foundation of China (National Science Foundation of China)(NSFC 81900965)