title: Biphasic influence of Miz1 on neural crest development by regulating cell survival and apical adhesion complex formation in the developing neural tube.
abstract: Myc interacting zinc finger protein-1 (Miz1) is a transcription factor known to regulate cell cycle- and cell adhesion-related genes in cancer. Here we show that Miz1 also plays a critical role in neural crest development. In the chick, Miz1 is expressed throughout the neural plate and closing neural tube. Its morpholino-mediated knockdown affects neural crest precursor survival, leading to reduction of neural plate border and neural crest specifier genes Msx-1, Pax7, FoxD3, and Sox10. Of interest, Miz1 loss also causes marked reduction of adhesion molecules (N-cadherin, cadherin6B, and α1-catenin) with a concomitant increase of E-cadherin in the neural folds, likely leading to delayed and decreased neural crest emigration. Conversely, Miz1 overexpression results in up-regulation of cadherin6B and FoxD3 expression in the neural folds/neural tube, leading to premature neural crest emigration and increased number of migratory crest cells. Although Miz1 loss effects cell survival and proliferation throughout the neural plate, the neural progenitor marker Sox2 was unaffected, suggesting a neural crest-selective effect. The results suggest that Miz1 is important not only for survival of neural crest precursors, but also for maintenance of integrity of the neural folds and tube, via correct formation of the apical adhesion complex therein.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Laura
authors.initials: L
authors.lastname: Kerosuo
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000096:biosynthesis / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002642:Chick Embryo; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D051957:MSX1 Transcription Factor / Q000235:genetics; D060172:Morpholinos / Q000235:genetics; D009420:Nervous System / Q000196:embryology*; D009432:Neural Crest / Q000196:embryology*; D054258:Neural Plate / Q000196:embryology; D054259:Neural Tube / Q000196:embryology*; D055495:Neurogenesis / Q000235:genetics*; D051763:PAX7 Transcription Factor / Q000235:genetics; D055748:SOXB1 Transcription Factors; D055757:SOXE Transcription Factors / Q000235:genetics; D051178:alpha Catenin / Q000096:biosynthesis
chemical_list: D030161:Avian Proteins; D015820:Cadherins; D051858:Forkhead Transcription Factors; D051741:Kruppel-Like Transcription Factors; D051957:MSX1 Transcription Factor; D060172:Morpholinos; D051763:PAX7 Transcription Factor; D055748:SOXB1 Transcription Factors; D055757:SOXE Transcription Factors; D051178:alpha Catenin; C094293:cad6B protein, Gallus gallus; C071559:Hbox 7 protein, Gallus gallus