Fox proteins are modular competency factors for facial cartilage and tooth specification

ABSTRACT Facial form depends on the precise positioning of cartilage, bone, and tooth fields in the embryonic pharyngeal arches. How complex signaling information is integrated to specify these cell types remains a mystery. We find that modular expression of Forkhead domain transcription factors (Fox proteins) in the zebrafish face arises through integration of Hh, Fgf, Bmp, Edn1 and Jagged-Notch pathways. Whereas loss of C-class Fox proteins results in reduced upper facial cartilages, loss of F-class Fox proteins results in distal jaw truncations and absent midline cartilages and teeth. We show that Fox proteins are required for Sox9a to promote chondrogenic gene expression. Fox proteins are sufficient in neural crest-derived cells for cartilage development, and neural crest-specific misexpression of Fox proteins expands the cartilage domain but inhibits bone. These results support a modular role for Fox proteins in establishing the competency of progenitors to form cartilage and teeth in the face. Highlighted Article: Combinatorial mutagenesis studies reveal that a large family of Forkhead transcription factors integrate diverse signaling outputs to specify distinct cartilages and teeth in the developing zebrafish face.

[1]  M. Bonaguidi,et al.  Genome-wide analysis of facial skeletal regionalization in zebrafish , 2017, Development.

[2]  B. de Crombrugghe,et al.  A Novel Regulatory Mechanism of Type II Collagen Expression via a SOX9-dependent Enhancer in Intron 6* , 2016, The Journal of Biological Chemistry.

[3]  J. Postlethwait,et al.  Ancient origin of lubricated joints in bony vertebrates , 2016, eLife.

[4]  J. Crump,et al.  Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration , 2016, Development.

[5]  Elizabeth Zuniga,et al.  Competition between Jagged-Notch and Endothelin1 Signaling Selectively Restricts Cartilage Formation in the Zebrafish Upper Face , 2016, PLoS genetics.

[6]  Han Liu,et al.  A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development , 2016, PLoS genetics.

[7]  A. McMahon,et al.  Iroquois Proteins Promote Skeletal Joint Formation by Maintaining Chondrocytes in an Immature State. , 2015, Developmental cell.

[8]  A. McMahon,et al.  Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte. , 2015, Cell reports.

[9]  T. Yoneda,et al.  The transcription factor Foxc1 is necessary for Ihh–Gli2-regulated endochondral ossification , 2015, Nature Communications.

[10]  L. Yin,et al.  The versatile functions of Sox9 in development, stem cells, and human diseases , 2014, Genes & diseases.

[11]  J. Crump,et al.  Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a , 2014, Development.

[12]  T. Kume,et al.  Interaction between Foxc1 and Fgf8 during Mammalian Jaw Patterning and in the Pathogenesis of Syngnathia , 2013, PLoS genetics.

[13]  C. Kimmel,et al.  barx1 represses joints and promotes cartilage in the craniofacial skeleton , 2013, Development.

[14]  Jingjing Sun,et al.  Foxc1 controls the growth of the murine frontal bone rudiment by direct regulation of a Bmp response threshold of Msx2 , 2013, Development.

[15]  Daniel Meulemans Medeiros,et al.  New perspectives on pharyngeal dorsoventral patterning in development and evolution of the vertebrate jaw. , 2012, Developmental biology.

[16]  D. Raible,et al.  Bmps and Id2a Act Upstream of Twist1 To Restrict Ectomesenchyme Potential of the Cranial Neural Crest , 2012, PLoS genetics.

[17]  Li-En Jao,et al.  A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization , 2012, Development.

[18]  D. Stainier,et al.  Analysis of sphingosine-1-phosphate signaling mutants reveals endodermal requirements for the growth but not dorsoventral patterning of jaw skeletal precursors. , 2012, Developmental biology.

[19]  Neville E Sanjana,et al.  A transcription activator-like effector toolbox for genome engineering , 2012, Nature Protocols.

[20]  Ken W. Y. Cho,et al.  Combinatorial roles for BMPs and Endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton , 2011, Development.

[21]  Thomas F Schilling,et al.  Gremlin 2 regulates distinct roles of BMP and Endothelin 1 signaling in dorsoventral patterning of the facial skeleton , 2011, Development.

[22]  M. Westerfield,et al.  Zebrafish sp7:EGFP: A transgenic for studying otic vesicle formation, skeletogenesis, and bone regeneration , 2010, Genesis.

[23]  Stephen L. Johnson,et al.  hand2 and Dlx genes specify dorsal, intermediate and ventral domains within zebrafish pharyngeal arches , 2010, Development.

[24]  Frank Stellabotte,et al.  Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face , 2010, Development.

[25]  Jian Xu,et al.  Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cells. , 2009, Genes & development.

[26]  Z. Tümer,et al.  PRACTICAL GENETICS In association with Axenfeld – Rieger syndrome and spectrum of PITX 2 and FOXC 1 mutations , 2009 .

[27]  Melissa Hardy,et al.  The Tol2kit: A multisite gateway‐based construction kit for Tol2 transposon transgenesis constructs , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[28]  Mb Walker,et al.  A two-color acid-free cartilage and bone stain for zebrafish larvae , 2007, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[29]  C. Kimmel,et al.  Zebrafish furin mutants reveal intricacies in regulating Endothelin1 signaling in craniofacial patterning. , 2006, Developmental biology.

[30]  P. Carlsson,et al.  Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production , 2006, Development.

[31]  A. Ghysen,et al.  Cell proliferation in the developing lateral line system of zebrafish embryos , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[32]  Catherine A. Wilson,et al.  A pair of Sox: distinct and overlapping functions of zebrafish sox9 co-orthologs in craniofacial and pectoral fin development , 2005, Development.

[33]  M. Jamrich,et al.  Function and regulation of FoxF1 during Xenopus gut development , 2004, Development.

[34]  Toyoaki Tenzen,et al.  Hedgehog signaling in the neural crest cells regulates the patterning and growth of facial primordia. , 2004, Genes & development.

[35]  D. Rowitch,et al.  Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Tao Wang,et al.  Forkhead transcription factor Foxf2 (LUN)-deficient mice exhibit abnormal development of secondary palate. , 2003, Developmental biology.

[37]  C. Kimmel,et al.  Two endothelin 1 effectors, hand2 and bapx1, pattern ventral pharyngeal cartilage and the jaw joint , 2003, Development.

[38]  D. Srivastava,et al.  Tbx1 is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer. , 2003, Genes & development.

[39]  J. Postlethwait,et al.  A zebrafish sox9 gene required for cartilage morphogenesis. , 2002, Development.

[40]  Marie-Christine Chaboissier,et al.  The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. , 2002, Genes & development.

[41]  B. Hogan,et al.  The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis. , 2001, Genes & development.

[42]  M. W. Glynn,et al.  Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. , 2000, American journal of human genetics.

[43]  C. Kimmel,et al.  sucker encodes a zebrafish Endothelin-1 required for ventral pharyngeal arch development. , 2000, Development.

[44]  D. Srivastava,et al.  Conservation of sequence and expression of Xenopus and zebrafish dHAND during cardiac, branchial arch and lateral mesoderm development , 2000, Mechanisms of Development.

[45]  K. Zaret,et al.  An early developmental transcription factor complex that is more stable on nucleosome core particles than on free DNA. , 1999, Molecular cell.

[46]  Richard R. Behringer,et al.  Sox9 is required for cartilage formation , 1999, Nature Genetics.

[47]  H. Hong,et al.  Pleiotropic skeletal and ocular phenotypes of the mouse mutation congenital hydrocephalus (ch/Mf1) arise from a winged helix/forkhead transcriptionfactor gene. , 1999, Human molecular genetics.

[48]  J. Campos-Ortega,et al.  Use of the Gal4-UAS technique for targeted gene expression in the zebrafish , 1999, Mechanisms of Development.

[49]  J. Morissette,et al.  Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. , 1998, American journal of human genetics.

[50]  B. Hogan,et al.  The Forkhead/Winged Helix Gene Mf1 Is Disrupted in the Pleiotropic Mouse Mutation congenital hydrocephalus , 1998, Cell.

[51]  T. Sugiyama,et al.  Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis. , 1997, Development.

[52]  P N Goodfellow,et al.  SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(II) collagen gene , 1997, Molecular and cellular biology.

[53]  C. Kimmel,et al.  Stages of embryonic development of the zebrafish , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[54]  Stephen L. Johnson,et al.  Differential induction of four msx homeobox genes during fin development and regeneration in zebrafish. , 1995, Development.

[55]  M. Westerfield,et al.  Combinatorial expression of three zebrafish genes related to distal- less: part of a homeobox gene code for the head , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.