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Critical Reviews in Oral Biology & Medicine
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11(3):304-317 (2000)     Crit Rev Oral Biol Med
© 2000 SAGE Publications

Genetic and Teratogenic Approaches To Craniofacial Development

D.L. Young

Department of Orthopaedic Surgery, School of Medicine, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514, Department of Growth and Development, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514

R.A. Schneider

Department of Orthopaedic Surgery, School of Medicine, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514, Department of Growth and Development, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514

D. Hu

Department of Orthopaedic Surgery, School of Medicine, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514, Department of Growth and Development, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514

J.A. Helms

Department of Orthopaedic Surgery, School of Medicine, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514, Department of Growth and Development, School of Dentistry, University of California at San Francisco, 533 Parnassus Ave., U-453, San Francisco, CA 94143-0514, helms{at}cgl.ucsf.edu

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 (TGFβ3). 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.

Key Words: Facial primordia • cleft lip/palate • gene knockouts • retinoic acid • Shh • Dix • EGFR • TGFβ3 • birth defects.

Critical Reviews in Oral Biology & Medicine, Vol. 11, No. 3, 304-317 (2000)
DOI: 10.1177/10454411000110030201
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