Postnatal lethality in mice lacking the Sax2 homeobox gene homologous to Drosophila S59/slouch: evidence for positive and negative autoregulation.
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.
Simon
Ruth
R
Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
Lufkin
Thomas
T
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*
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C109095:Nkx1-2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C066818:slou protein, Drosophila