Misexpression of a bHLH gene, cNSCL1, results in abnormal brain development.
NSCL1 is a basic helix-loop-helix transcription factor involved in the development of the nervous system. To elucidate its role in neurogenesis, we cloned chick NSCL1 (cNSCL1) and examined its expression pattern and the effect of its misexpression on brain development. cNSCL1 was predominantly expressed during active neurogenesis. Double-labeling experiments showed that proliferating neuroblasts in the ventricular zone lacked cNSCL1 expression and cells expressing cNSCL1 were located just outside the ventricular zone. Retroviral misexpression of cNSCL1 in chick embryos produced a brain with abnormal structure. While the forebrain of the embryonic day-12 (E12) brain appeared normal, the tectum was enlarged. The enlargement was likely due to an increase in cell proliferation, since more radioactivity was detected in this region of the brain after [3H]thymidine labeling at E9. The cerebellum, on the other hand, was reduced in size. Fewer cells were labeled with BrdU in the external granule layer (a secondary germinal layer required for cerebellum development) in experimental embryos than in the controls, suggesting that misexpression of cNSCL1 might interfere with cell proliferation in the external granular layer. Our data indicate that regulated expression of cNSCL1 is required for normal brain development. They also imply that cNSCL1 might be involved in preventing some postmitotic cells from reentering the cell cycle during neurogenesis. Dev Dyn 1999;215:238-247.
Department of Ophthalmology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35233, USA.
C M
CM
Li
R T
RT
Yan
S Z
SZ
Wang
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D002453:Cell Cycle; D002531:Cerebellum / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008845:Microinjections; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016548:Prosencephalon / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013047:Specific Pathogen-Free Organisms; D013477:Superior Colliculi / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C076746:NHLH1 protein, human