About face: signals and genes controlling jaw patterning and identity in vertebrates.

The embryonic vertebrate face is composed of similarly sized buds of neural crest-derived mesenchyme encased in epithelium. These buds or facial prominences grow and fuse together to give the postnatal morphology characteristic of each species. Here we review the role of neural crest cells and foregut endoderm in differentiating facial features. We relate the developing facial prominences to the skeletal structure of the face and review the signals and genes that have been shown to play an important role in facial morphogenesis. We also examine two experiments one at the genetic level and one at the signal level in which transformation of facial prominences and subsequent change of jaw identity was induced. We propose that signals such as retinoids and BMPs and downstream transcription factors such as Distal-less related genes specify jaw identity.

[1]  Shigeru Kuratani,et al.  Heterotopic Shift of Epithelial-Mesenchymal Interactions in Vertebrate Jaw Evolution , 2002, Science.

[2]  V. Papaioannou,et al.  DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1 , 2001, Nature Genetics.

[3]  Kathryn W. Tosney.  The segregation and early migration of cranial neural crest cells in the avian embryo. , 1982, Developmental biology.

[4]  J. Rubenstein,et al.  Independent regulation of Dlx2 expression in the epithelium and mesenchyme of the first branchial arch. , 2000, Development.

[5]  J. Murray,et al.  Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. , 1997, Human molecular genetics.

[6]  K. Yamamura,et al.  Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse. , 2002, Development.

[7]  R. Krumlauf,et al.  Plasticity in mouse neural crest cells reveals a new patterning role for cranial mesoderm , 2000, Nature Cell Biology.

[8]  S. Aizawa,et al.  Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice. , 2002, Development.

[9]  R. Kosher,et al.  Wnt-5a and Wnt-7a are expressed in the developing chick limb bud in a manner suggesting roles in pattern formation along the proximodistal and dorsoventral axes , 1993, Mechanisms of Development.

[10]  G. Boivin,et al.  TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. , 1997, Development.

[11]  B. Hall,et al.  The in vivo and in vitro effects of bone morphogenetic protein-2 on the development of the chick mandible. , 1997, The International journal of developmental biology.

[12]  P. Chambon,et al.  Embryonic retinoic acid synthesis is essential for early mouse post-implantation development , 1999, Nature Genetics.

[13]  M. Kessel,et al.  Ectodermal patterning in the avian embryo: epidermis versus neural plate. , 1999, Development.

[14]  Y. Ouchi,et al.  Elevated blood pressure and craniofaclal abnormalities in mice deficient in endothelin-1 , 1994, Nature.

[15]  B. Hall,et al.  Role of the neural crest in development of the cartilaginous cranial and visceral skeleton of the medaka, Oryzias latipes (Teleostei) , 2004, Anatomy and Embryology.

[16]  H. Westphal,et al.  Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene lhx8. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[17]  K. Weiss,et al.  Expression of Dlx genes during the development of the murine dentition , 2000, Development Genes and Evolution.

[18]  J. Rubenstein,et al.  Association of MSX1 and TGFB3 with nonsyndromic clefting in humans. , 1998, American journal of human genetics.

[19]  P. Scambler,et al.  Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice , 2001, Nature.

[20]  R. Behringer,et al.  Goosecoid is not an essential component of the mouse gastrula organizer but is required for craniofacial and rib development. , 1995, Development.

[21]  R. Jaenisch,et al.  Transcription factor AP-2 essential for cranial closure and craniofacial development , 1996, Nature.

[22]  A. Bloch-Zupan,et al.  The variable expressivity and incomplete penetrance of the twist-null heterozygous mouse phenotype resemble those of human Saethre-Chotzen syndrome. , 1998, Human molecular genetics.

[23]  P. Francis-West,et al.  Expression patterns of the bone morphogenetic protein genes Bmp‐4 and Bmp‐2 in the developing chick face suggest a role in outgrowth of the primordia , 1994, Developmental dynamics : an official publication of the American Association of Anatomists.

[24]  M. Cohen,et al.  Malformations of the craniofacial region: evolutionary, embryonic, genetic, and clinical perspectives. , 2002, American journal of medical genetics.

[25]  Concepción Rodríguez-Esteban,et al.  Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesis and pituitary development. , 1999, Genes & development.

[26]  J. Richman,et al.  Expression of fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3) in the developing head and face , 1997, Developmental dynamics : an official publication of the American Association of Anatomists.

[27]  Georgy Koentges,et al.  Neural Crest Apoptosis and the Establishment of Craniofacial Pattern: An Honorable Death , 1996, Molecular and Cellular Neuroscience.

[28]  G. Robinson,et al.  Differential and overlapping expression domains of Dlx-2 and Dlx-3 suggest distinct roles for Distal-less homeobox genes in craniofacial development , 1994, Mechanisms of Development.

[29]  Yuan-qing Wu,et al.  Familial case of Potocki–Shaffer syndrome associated with microdeletion of EXT2 and ALX4 , 2001, Clinical genetics.

[30]  A. McMahon,et al.  Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2 , 1996, Nature.

[31]  P. Patel,et al.  Mutation of PAX9 is associated with oligodontia , 2000, Nature Genetics.

[32]  P. Sharpe,et al.  Temporospatial cell interactions regulating mandibular and maxillary arch patterning. , 2000, Development.

[33]  C. Marcelle,et al.  Ectodermal Wnt Function as a Neural Crest Inducer , 2002, Science.

[34]  K. von der Mark,et al.  Transient expression of collagen type II at epitheliomesenchymal interfaces during morphogenesis of the cartilaginous neurocranium. , 1986, Developmental biology.

[35]  D. Summerbell,et al.  Positional signalling and specification of digits in chick limb morphogenesis , 1975, Nature.

[36]  F. Vitelli,et al.  Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest and cranial nerve migratory pathways. , 2002, Human molecular genetics.

[37]  C. Tickle,et al.  Alterations in Msx 1 and Msx 2 expression correlate with inhibition of outgrowth of chick facial primordia induced by retinoic acid , 1997, Anatomy and Embryology.

[38]  J. Clarke,et al.  Fate map of the developing chick face: Analysis of expansion of facial primordia and establishment of the primary palate , 1998, Developmental dynamics : an official publication of the American Association of Anatomists.

[39]  A. McMahon,et al.  Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. , 2000, Development.

[40]  M. Ferguson,et al.  Transforming growth factor–β3 is required for secondary palate fusion , 1995, Nature Genetics.

[41]  M. Bronner‐Fraser,et al.  Early- and late-migrating cranial neural crest cell populations have equivalent developmental potential in vivo. , 1997, Development.

[42]  Xiang Zhao,et al.  Transgenically ectopic expression of Bmp4 to the Msx1 mutant dental mesenchyme restores downstream gene expression but represses Shh and Bmp2 in the enamel knot of wild type tooth germ , 2000, Mechanisms of Development.

[43]  D. Noden.  The control of avian cephalic neural crest cytodifferentiation. II. Neural tissues. , 1978, Developmental biology.

[44]  G. Eichele,et al.  Sonic hedgehog participates in craniofacial morphogenesis and is down-regulated by teratogenic doses of retinoic acid. , 1997, Developmental biology.

[45]  S. Mackem,et al.  Soluble dominant‐negative receptor uncovers essential roles for fibroblast growth factors in multi‐organ induction and patterning , 1998, The EMBO journal.

[46]  J. Lawrenson,et al.  The 22q11.2 deletion: From diversity to a single gene theory , 2001, Genetics in Medicine.

[47]  Christine Vincent,et al.  Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton. , 2002, Development.

[48]  S. Wedden.  Epithelial-mesenchymal interactions in the development of chick facial primordia and the target of retinoid action. , 1987, Development.

[49]  A. Kawakami,et al.  Distributions of PAX6 and PAX7 proteins suggest their involvement in both early and late phases of chick brain development , 1997, Mechanisms of Development.

[50]  R. A. Schneider,et al.  The Cellular and Molecular Origins of Beak Morphology , 2003, Science.

[51]  S. Camper,et al.  The bicoid-related Pitx gene family in development , 1999, Mammalian Genome.

[52]  S. Kuratani,et al.  Ectodermally derived FGF8 defines the maxillomandibular region in the early chick embryo: epithelial-mesenchymal interactions in the specification of the craniofacial ectomesenchyme. , 2000, Developmental biology.

[53]  M. Depew,et al.  Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. , 1999, Genes & development.

[54]  P. Sharpe,et al.  Transformation of tooth type induced by inhibition of BMP signaling. , 1998, Science.

[55]  R. E. Shore.  An electrophoretic analysis of proteins of cellular sap in normal and hybrid frog embryos. , 1965, Journal of embryology and experimental morphology.

[56]  E. Lammer,et al.  Retinoic acid embryopathy: case report and review of literature. , 1996, Pediatric pathology & laboratory medicine : journal of the Society for Pediatric Pathology, affiliated with the International Paediatric Pathology Association.

[57]  R. Behringer,et al.  twist is required in head mesenchyme for cranial neural tube morphogenesis. , 1995, Genes & development.

[58]  E. Kollar,et al.  The induction of odontogenesis in non-dental mesenchyme combined with early murine mandibular arch epithelium. , 1987, Archives of oral biology.

[59]  J. Martín,et al.  prx-1 functions cooperatively with another paired-related homeobox gene, prx-2, to maintain cell fates within the craniofacial mesenchyme. , 1999, Development.

[60]  S. Scherer,et al.  Genetic analysis of patients with the Saethre-Chotzen phenotype. , 2002, American journal of medical genetics.

[61]  K. Fu,et al.  Noggin and retinoic acid transform the identity of avian facial prominences , 2001, Nature.

[62]  A. Neubüser,et al.  Expression of members of the Fgf family and their receptors during midfacial development , 2001, Mechanisms of Development.

[63]  K. Yasuda,et al.  Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds , 1999, Nature.

[64]  S. Scherer,et al.  Characterization of the split hand/split foot malformation locus SHFM1 at 7q21.3-q22.1 and analysis of a candidate gene for its expression during limb development. , 1996, Human molecular genetics.

[65]  J. Lim,et al.  Differential regulation of Dlx gene expression by a BMP morphogenetic gradient. , 2001, The International journal of developmental biology.

[66]  S. Aizawa,et al.  Mouse Otx2 functions in the formation and patterning of rostral head. , 1995, Genes & development.

[67]  Mahlon D. Johnson,et al.  Expression of Transforming Growth Factor-β1, -β2, and -β3 mRNA and Protein in the Murine Lung , 1991 .

[68]  Xiang Zhao,et al.  Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. , 2002, Development.

[69]  K. Fu,et al.  Endogenous bone morphogenetic proteins regulate outgrowth and epithelial survival during avian lip fusion. , 2002, Development.

[70]  J. Rubenstein,et al.  Local retinoid signaling coordinates forebrain and facial morphogenesis by maintaining FGF8 and SHH. , 2001, Development.

[71]  S. Aizawa,et al.  Development of cephalic neural crest cells in embryos of Lampetra japonica, with special reference to the evolution of the jaw. , 1999, Developmental biology.

[72]  S. Iseki,et al.  Tissue origins and interactions in the mammalian skull vault. , 2002, Developmental biology.

[73]  L. Silver,et al.  Expression of the T‐box family genes, Tbx1–Tbx5, during early mouse development , 1996, Developmental dynamics : an official publication of the American Association of Anatomists.

[74]  L. Silver,et al.  Expression of T-box genes Tbx2–Tbx5 during chick organogenesis , 1998, Mechanisms of Development.

[75]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. , 1994, Development.

[76]  R. Krumlauf,et al.  Deciphering the Hox code: Clues to patterning branchial regions of the head , 1991, Cell.

[77]  P. Gruss,et al.  Dysgenesis of cephalic neural crest derivatives in Pax7-/- mutant mice. , 1996, Development.

[78]  C. Lanctôt,et al.  Hindlimb patterning and mandible development require the Ptx1 gene. , 1999, Development.

[79]  B. Devlin,et al.  Fine mapping of the split-hand/split-foot locus (SHFM3) at 10q24: evidence for anticipation and segregation distortion. , 1999, American journal of human genetics.

[80]  C. Tabin,et al.  Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity. , 1999, Science.

[81]  C. Tickle,et al.  Epithelia are interchangeable between facial primordia of chick embryos and morphogenesis is controlled by the mesenchyme. , 1989, Developmental biology.

[82]  J. Richman,et al.  Effect of fibroblast growth factors on outgrowth of facial mesenchyme. , 1997, Developmental biology.

[83]  P. Chambon,et al.  Differential expression of retinoic acid-synthesizing (RALDH) enzymes during fetal development and organ differentiation in the mouse , 2002, Mechanisms of Development.

[84]  V. Kaartinen,et al.  Abnormal lung development and cleft palate in mice lacking TGF–β3 indicates defects of epithelial–mesenchymal interaction , 1995, Nature Genetics.

[85]  A. Graham,et al.  Segmental origin and migration of neural crest cells in the hindbrain region of the chick embryo. , 1991, Development.

[86]  Mina Mina,et al.  Region‐ and stage‐specific effects of FGFs and BMPs in chick mandibular morphogenesis , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[87]  P. Sharpe,et al.  Fgf-8 determines rostral-caudal polarity in the first branchial arch. , 1999, Development.

[88]  A. Joyner,et al.  Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm- and mesoderm-derived tissues suggests multiple roles during postimplantation development. , 1994, Developmental biology.

[89]  G. Merlo,et al.  Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5. , 1999, Development.

[90]  A. Knecht,et al.  Induction of the neural crest: a multigene process , 2002, Nature Reviews Genetics.

[91]  S. Camper,et al.  Dosage requirement of Pitx2 for development of multiple organs. , 1999, Development.

[92]  A. Lumsden,et al.  Rhombencephalic neural crest segmentation is preserved throughout craniofacial ontogeny. , 1996, Development.

[93]  K. Sugimura,et al.  Nasal and pharyngeal abnormalities caused by the mouse goosecoid gene mutation. , 1997, Biochemical and biophysical research communications.

[94]  Nicole Firnberg,et al.  FGF signaling regulates expression of Tbx2, Erm, Pea3, and Pax3 in the early nasal region. , 2002, Developmental biology.

[95]  J. Martín,et al.  The paired-like homeo box gene MHox is required for early events of skeletogenesis in multiple lineages. , 1995, Genes & development.

[96]  V. Prince,et al.  Hoxa-2 expression in normal and transposed rhombomeres: independent regulation in the neural tube and neural crest. , 1994, Development.

[97]  M. Muenke,et al.  Human developmental disorders and the Sonic hedgehog pathway. , 1998, Molecular medicine today.

[98]  A. McMahon,et al.  Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. , 2001, Development.

[99]  A. McMahon,et al.  Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. , 1998, Science.

[100]  P. Goodfellow,et al.  The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia , 2001, Nature Genetics.

[101]  P. Janvier,et al.  Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation: Mirror of the past? , 2002, Genesis.

[102]  K. Kratochwil,et al.  Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. , 1998, Genes & development.

[103]  R. Hammer,et al.  Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme-1 gene. , 1998, Development.

[104]  I. Thesleff,et al.  Reiterative signaling and patterning during mammalian tooth morphogenesis , 2000, Mechanisms of Development.

[105]  T. Kornberg,et al.  Cytonemes Cellular Processes that Project to the Principal Signaling Center in Drosophila Imaginal Discs , 1999, Cell.

[106]  V. Hamburger,et al.  A series of normal stages in the development of the chick embryo. 1951. , 2012, Developmental dynamics : an official publication of the American Association of Anatomists.

[107]  C. Tickle,et al.  Epithelial-mesenchymal interactions in the outgrowth of limb buds and facial primordia in chick embryos. , 1992, Developmental biology.

[108]  J. Richman,et al.  Chicken transcription factor AP-2: cloning, expression and its role in outgrowth of facial prominences and limb buds. , 1997, Developmental biology.

[109]  Christine Vincent,et al.  Interactions between Hox-negative cephalic neural crest cells and the foregut endoderm in patterning the facial skeleton in the vertebrate head. , 2002, Development.

[110]  J. Rubenstein,et al.  Role of the Dlx homeobox genes in proximodistal patterning of the branchial arches: mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 alter morphogenesis of proximal skeletal and soft tissue structures derived from the first and second arches. , 1997, Developmental biology.

[111]  R. Hammer,et al.  Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice. , 1998, Development.

[112]  F. Beemer,et al.  MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans , 2000, Nature Genetics.

[113]  Ryan M. Anderson,et al.  The organizer factors Chordin and Noggin are required for mouse forebrain development , 2000, Nature.

[114]  U. Dräger,et al.  Differential distribution of retinoic acid synthesis in the chicken embryo as determined by immunolocalization of the retinoic acid synthetic enzyme, RALDH-2. , 1999, Developmental biology.

[115]  R. Maas,et al.  Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation , 2000, Nature Genetics.

[116]  J. Korving,et al.  Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice. , 2001, Development.

[117]  H. Heng,et al.  Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development. , 1997, Development.

[118]  H. Shibuya,et al.  A BMP-inducible gene, dlx5, regulates osteoblast differentiation and mesoderm induction. , 1999, Developmental biology.

[119]  R. Krumlauf,et al.  Role of the Isthmus and FGFs in Resolving the Paradox of Neural Crest Plasticity and Prepatterning , 2002, Science.

[120]  N M Le Douarin,et al.  The triple origin of skull in higher vertebrates: a study in quail-chick chimeras. , 1993, Development.

[121]  Moisés Mallo,et al.  Hoxa-2 mutant mice exhibit homeotic transformation of skeletal elements derived from cranial neural crest , 1993, Cell.

[122]  Pierre Chambon,et al.  A homeotic transformation is generated in the rostral branchial region of the head by disruption of Hoxa-2, which acts as a selector gene , 1993, Cell.

[123]  P J Bryant,et al.  A new family of growth factors produced by the fat body and active on Drosophila imaginal disc cells. , 1999, Development.

[124]  R. Maas,et al.  Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development , 1994, Nature Genetics.

[125]  C. Cremers,et al.  Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis , 1999, Nature Genetics.

[126]  Thomas Lufkin,et al.  Specification of Jaw Subdivisions by Dlx Genes , 2002, Science.

[127]  J. Rubenstein,et al.  Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain. , 1995, Genes & development.

[128]  M. Patton,et al.  Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients. , 2002, Human molecular genetics.

[129]  M. Yanagisawa,et al.  Signaling pathways crucial for craniofacial development revealed by endothelin-A receptor-deficient mice. , 2000, Developmental biology.

[130]  I. Thesleff,et al.  Responsiveness of developing dental tissues to fibroblast growth factors: expression of splicing alternatives of FGFR1, -2, -3, and of FGFR4; and stimulation of cell proliferation by FGF-2, -4, -8, and -9. , 1998, Developmental genetics.

[131]  D M Noden,et al.  The role of the neural crest in patterning of avian cranial skeletal, connective, and muscle tissues. , 1983, Developmental biology.

[132]  G. Eichele,et al.  The expression pattern of the chick homeobox gene gMHox suggests a role in patterning of the limbs and face and in compartmentalization of somites. , 1994, Developmental biology.

[133]  Randy L. Johnson,et al.  Function of Rieger syndrome gene in left–right asymmetry and craniofacial development , 1999, Nature.

[134]  Concepción Rodríguez-Esteban,et al.  The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity , 1999, Nature.

[135]  P. Chambon,et al.  Retinaldehyde dehydrogenase 2 (RALDH2)- independent patterns of retinoic acid synthesis in the mouse embryo , 2002, Proceedings of the National Academy of Sciences of the United States of America.