title: A morpholino-based screen to identify novel genes involved in craniofacial morphogenesis.
abstract: BACKGROUND
  The regulatory mechanisms underpinning facial development are conserved between diverse species. Therefore, results from model systems provide insight into the genetic causes of human craniofacial defects. Previously, we generated a comprehensive dataset examining gene expression during development and fusion of the mouse facial prominences. Here, we used this resource to identify genes that have dynamic expression patterns in the facial prominences, but for which only limited information exists concerning developmental function.
  
  
  RESULTS
  This set of ∼80 genes was used for a high-throughput functional analysis in the zebrafish system using Morpholino gene knockdown technology. This screen revealed three classes of cranial cartilage phenotypes depending upon whether knockdown of the gene affected the neurocranium, viscerocranium, or both. The targeted genes that produced consistent phenotypes encoded proteins linked to transcription (meis1, meis2a, tshz2, vgll4l), signaling (pkdcc, vlk, macc1, wu:fb16h09), and extracellular matrix function (smoc2). The majority of these phenotypes were not altered by reduction of p53 levels, demonstrating that both p53-dependent and -independent mechanisms were involved in the craniofacial abnormalities.
  
  
  CONCLUSIONS
  This Morpholino-based screen highlights new genes involved in development of the zebrafish craniofacial skeleton with wider relevance to formation of the face in other species, particularly mouse and human.
authors.affiliation: Department of Craniofacial Biology, School of Dental Medicine, University of Colorado, Denver, Colorado, USA.
authors.forename: Vida Senkus
authors.initials: VS
authors.lastname: Melvin
authors.forename: Weiguo
authors.initials: W
authors.lastname: Feng
authors.forename: Laura
authors.initials: L
authors.lastname: Hernandez-Lagunas
authors.forename: Kristin Bruk
authors.initials: KB
authors.lastname: Artinger
authors.forename: Trevor
authors.initials: T
authors.lastname: Williams
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005147:Facial Bones / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D060172:Morpholinos; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000196:embryology* / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D060172:Morpholinos; C102641:Mrg1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C513851:SMOC-2 protein, mouse; C489362:Tshz2 protein, mouse; D029961:Zebrafish Proteins
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