Dorsal and lateral fates in the mouse neural tube require the cell-autonomous activity of the open brain gene.
The processes that specify early regional identity in dorsal and lateral regions of the mammalian neural tube are not well understood. The mouse open brain (opb) gene plays an essential role in dorsal neural patterning: in the caudal spinal cord of opb mutants, dorsal cell types are absent and markers of ventral fates, including Shh, expand into dorsal regions. Analysis of the opb mutant phenotype and of opb/opb <--> wild-type chimeric embryos reveals that early in neural development, the wild-type opb gene (opb(+)) is required cell autonomously for the expression of Pax7 in dorsal cells and Pax6 in lateral cells. Thus the opb(+) gene product acts intracellularly in the reception or interpretation of signals that determine cell types in the dorsal 80% of the neural tube. At later stages, the lack of opb(+) causes a non-cell-autonomous expansion of ventral cell types into dorsal regions of the neural tube, revealing that opb(+) controls the production of a diffusible molecule that defines the domain of Shh expression. The data indicate that opb(+) could act as either a novel component of a dorsalizing pathway or a novel intracellular negative regulator of the Shh signal transduction pathway.
Eggenschwiler
J T
JT
Molecular Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA.
Anderson
K V
KV
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism; D002678:Chimera; D004268:DNA-Binding Proteins / Q000235:genetics; D005136:Eye Proteins; D005796:Genes; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D051957:MSX1 Transcription Factor; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008959:Models, Neurological; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D001616:beta-Galactosidase / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; D000071841:PAX6 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C497322:Pax7 protein, mouse; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D001616:beta-Galactosidase