title: A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face.
abstract: The mechanisms of morphogenesis are not well understood, yet shaping structures during development is essential for establishing correct organismal form and function. Here, we examine mechanisms that help to shape the developing face during the crucial period of facial primordia fusion. This period of development is a time when the faces of amniote embryos exhibit the greatest degree of similarity, and it probably results from the necessity for fusion to occur to establish the primary palate. Our results show that hierarchical induction mechanisms, consisting of iterative signaling by Sonic hedgehog (SHH) followed by Bone morphogenetic proteins (BMPs), regulate a dynamic expression pattern of Shh in the ectoderm covering the frontonasal (FNP) and maxillary (MxP) processes. Furthermore, this Shh expression domain contributes to the morphogenetic processes that drive the directional growth of the globular process of the FNP toward the lateral nasal process and MxP, in part by regulating cell proliferation in the facial mesenchyme. The nature of the induction mechanism that we discovered suggests that the process of fusion of the facial primordia is intrinsically buffered against producing maladaptive morphologies, such as clefts of the primary palate, because there appears to be little opportunity for variation to occur during expansion of the Shh expression domain in the ectoderm of the facial primordia. Ultimately, these results might explain why this period of development constitutes a phylotypic stage of facial development among amniotes.
authors.affiliation: Department of Orthopaedic Surgery, San Francisco General Hospital, Orthopaedic Trauma Institute, The University of California at San Francisco, School of Medicine, San Francisco, CA 94110, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, San Francisco General Hospital, Orthopaedic Trauma Institute, The University of California at San Francisco, School of Medicine, San Francisco, CA 94110, USA.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Young
authors.affiliation: Department of Orthopaedic Surgery, San Francisco General Hospital, Orthopaedic Trauma Institute, The University of California at San Francisco, School of Medicine, San Francisco, CA 94110, USA National Key Laboratory of Bio-Macromolecule, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, San Francisco General Hospital, Orthopaedic Trauma Institute, The University of California at San Francisco, School of Medicine, San Francisco, CA 94110, USA Epitomizes, Inc., 1418 Moganshan Road, Hangzhou, Zhejiang 310011, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Anatomy and Cell Biology, University of Calgary, McCaig Institute for Bone and Joint Health, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hallgrímsson
authors.affiliation: Department of Orthopaedic Surgery, San Francisco General Hospital, Orthopaedic Trauma Institute, The University of California at San Francisco, School of Medicine, San Francisco, CA 94110, USA marcucio@orthosurg.ucsf.edu.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Marcucio
mesh_terms: D000818:Animals; D001837:Body Weights and Measures; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002642:Chick Embryo; D005145:Face / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D009024:Morphogenesis / Q000502:physiology*; D010159:Palate / Q000196:embryology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D001973:Bromodeoxyuridine
keywords: BMP; Chick; Cleft lip and palate; Craniofacial development; Facial fusion; Frontonasal ectodermal zone; Mouse; SHH