title: Rieger syndrome revisited: experimental approaches using pharmacologic and antisense strategies to abrogate EGF and TGF-alpha functions resulting in dysmorphogenesis during embryonic mouse craniofacial morphogenesis.
abstract: The major manifestations of Rieger syndrome (RS), an autosomal dominant disorder, include absent maxillary incisor teeth, malformations of the anterior chamber of the eye, and umbilical anomalies [Aarskog et al., 1983: Am J Med Genet 15:29-38; Gorlin et al., 1990: "Syndromes of the Head and Neck" 3rd ed.]. Linkage of RS to human chromosome 4q markers has been identified with tight linkage to epidermal growth factor (EGF) [Murray et al., 1992: Nat Genet 2:46-48]. Mutations associated with genes of the EGF superfamily are implicated in malformations arising from abnormal development of the first branchial arch [Ardinger et al., 1989: Am J Hum Genet 45:348-353; Sassani et al., 1993: Am J Med Genet 45:565-569]. Down-regulation of EGF during early mouse development results in ablation of tooth formation [Kronmiller et al., 1991: Dev Biol 147:485-488]. Since EGF, TGF-alpha, and EGF receptor (EGFr) transcripts are expressed in the mouse first branchial arch and derivatives, experimental strategies were employed to investigate the consequences of down-regulation of EGF translation and inhibition of EGF receptor during embryonic mandibular morphogenesis. Antisense inhibition of EGF expression produces mandibular dysmorphogenesis with decreased tooth bud size; these effects are reversed by the addition of exogenous EGF to the culture medium [Shum et al., 1993: Development 118:903-917]. Tyrphostin RG 50864, which inhibits EGF receptor kinase activity, inhibits EGF or TGF-alpha stimulation of tyrosine phosphorylation in a concentration-dependent manner and severely retards mandibular development [Shum et al., 1993: Development 118:903-917].(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles 90033.
authors.forename: H C
authors.initials: HC
authors.lastname: Slavkin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002396:Catechols / Q000494:pharmacology; D016373:DNA, Antisense / Q000235:genetics; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000235:genetics / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005147:Facial Bones / Q000002:abnormalities* / Q000196:embryology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D012886:Skull / Q000002:abnormalities* / Q000196:embryology; D013577:Syndrome; D014071:Tooth Abnormalities / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics; D020032:Tyrphostins
chemical_list: D002396:Catechols; D016373:DNA, Antisense; D009570:Nitriles; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; C060152:tyrphostin 47; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases