Genetic and teratogenic approaches to craniofacial development.
Craniofacial malformations are the most common birth defects that occur in humans, with facial clefting representing the majority of these defects. Facial clefts can arise at any stage of development due to perturbations that alter the extracellular matrix as well as affect the patterning, migration, proliferation, and differentiation of cells. In this review, we focus on recent advances in the understanding of the developmental basis for facial clefting through the analysis of the effects of gene disruption experiments and treatments with teratogens in both chickens and mice. Specifically, we analyze the results of disruptions to genes such as Sonic hedgehog (Shh), epidermal growth factor receptor (EGFR), Distal-less (Dlx), and transforming growth factor beta 3 (TGFbeta3). We also describe the effects that teratogens such as retinoic acid, jervine, and cyclopamine have on facial clefting and discuss mechanisms for their action. In addition to providing insight into the bases for abnormal craniofacial growth, genetic and teratogenic techniques are powerful tools for understanding the normal developmental processes that generate and pattern the face.
Young
D L
DL
Department of Orthopaedic Surgery, School of Medicine, University of California at San Francisco, 94143-0514, USA.
Schneider
R A
RA
Hu
D
D
Helms
J A
JA
D000818:Animals; D002642:Chick Embryo; D002971:Cleft Lip / Q000196:embryology / Q000209:etiology / Q000235:genetics; D002972:Cleft Palate / Q000196:embryology* / Q000209:etiology / Q000235:genetics; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000502:physiology; D004627:Embryonic Induction; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000502:physiology; D008445:Maxillofacial Development / Q000187:drug effects; D051379:Mice; D011506:Proteins / Q000502:physiology; D016601:RNA-Binding Proteins; D012176:Retinoids / Q000633:toxicity; D012886:Skull / Q000196:embryology; D013723:Teratogens / Q000633:toxicity; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000502:physiology; D014704:Veratrum Alkaloids / Q000633:toxicity
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C088334:Distal-less homeobox proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D012176:Retinoids; D013723:Teratogens; C093661:Tes protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014704:Veratrum Alkaloids; C010206:jervine; C000541:cyclopamine