title: An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull.
abstract: The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure.
authors.affiliation: Department of Molecular Biosciences; Institute of Cell and Molecular Biology, Waggoner Center for Alcohol and Alcohol Addiction Research, University of Texas, Austin, TX, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: McCarthy
authors.affiliation: Department of Molecular Biosciences; Institute of Cell and Molecular Biology, Waggoner Center for Alcohol and Alcohol Addiction Research, University of Texas, Austin, TX, United States.
authors.forename: Alfire
authors.initials: A
authors.lastname: Sidik
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Julien Y
authors.initials: JY
authors.lastname: Bertrand
authors.affiliation: Department of Molecular Biosciences; Institute of Cell and Molecular Biology, Waggoner Center for Alcohol and Alcohol Addiction Research, University of Texas, Austin, TX, United States; Department of Molecular Biosciences; Institute of Neurobiology, University of Texas, Austin, TX, United States. Electronic address: eberhart@austin.utexas.edu.
authors.forename: Johann K
authors.initials: JK
authors.lastname: Eberhart
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D051518:Fibroblast Growth Factor 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D014453:Glucuronosyltransferase / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D000076002:Hyaluronan Synthases; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction; D012886:Skull / Q000196:embryology* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D051518:Fibroblast Growth Factor 3; D053823:Hedgehog Proteins; C524053:Shha protein, zebrafish; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; C517774:fgf8a protein, zebrafish; D005346:Fibroblast Growth Factors; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; C491095:has2 protein, zebrafish
keywords: Craniofacial development; Fgf; Head mesoderm; Shh; Zebrafish