Dual role of brain factor-1 in regulating growth and patterning of the cerebral hemispheres.
Brain factor-1 (BF-1) is a winged-helix (WH) transcription factor with a restricted pattern of expression in the neural tube. In the embryo, BF-1 is localized to the progenitor cells of the most rostral neural tube, the telencephalic neuroepithelium. Expression of BF-1 persists in the adult brain in the structures derived from the telencephalon, including the cerebral cortex, the hippocampus, the olfactory bulbs and the basal ganglia. Targeted disruption of the BF-1 gene in mice results in hypoplasia of the cerebral hemispheres. Proliferation of the telencephalic neuroepithelium is decreased and neuronal differentiation occurs prematurely. The forebrain of the BF-1 (-/-) mutant also displays dorsal-ventral patterning defects. Development of the ventral (basal) region of the telencephalon is more severely affected than the dorsal region. These anomalies are associated with the ectopic expression of BMP4 in the dorsal telencephalic neuroepithelium and the loss of shh in the ventral telencephalon. These results raise the possibility that BF-1 may modulate both progenitor cell proliferation and regional patterning by regulating the expression or activity of inductive signals which act on the telencephalic neuroepithelium.
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Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. c-dou@ski.mskcc.org
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D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D001923:Brain Chemistry / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007763:Lac Operon; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics; D019579:Neocortex / Q000737:chemistry* / Q000166:cytology / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C489562:Foxd1 protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D001616:beta-Galactosidase