title: Postnatal lethality in mice lacking the Sax2 homeobox gene homologous to Drosophila S59/slouch: evidence for positive and negative autoregulation.
abstract: Homeobox gene transcription factors direct multiple functions during development. They are involved in early patterning of the embryo as well as cell specification, cell differentiation, and organogenesis. Here we describe a previously uncharacterized murine homeobox gene, Sax2, that shows high similarity to the Drosophila S59/slouch and murine Sax1 genes. We show that Sax2 gene expression occurs early during embryogenesis in the midbrain, the midbrain-hindbrain boundary, the ventral neural tube, the developing eye, and the apical ectodermal ridge of the limb. To determine the role of Sax2 during development, we generated a knockout mouse line by replacing part of the Sax2 coding sequences with the lacZ gene. The Sax2 null allele mutants exhibit a strong phenotype indicated by growth retardation starting immediately after birth and leading to premature death within the first 3 weeks postnatal. Intriguingly, our studies also demonstrated a striking autoregulation of the Sax2 gene in both positive- and negative-feedback mechanisms depending on the specific cell type expressing Sax2.
authors.affiliation: Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Simon
authors.forename: Thomas
authors.initials: T
authors.lastname: Lufkin
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000196:embryology; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017344:Genes, Insect; D005804:Genes, Lethal; D018398:Homeodomain Proteins / Q000235:genetics*; D006706:Homeostasis; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics*; D010641:Phenotype; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C109095:Nkx1-2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C066818:slou protein, Drosophila