Necdin promotes tangential migration of neocortical interneurons from basal forebrain.
Necdin is a pleiotropic protein that promotes neuronal differentiation and survival. In mammals, the necdin gene on the maternal chromosome is silenced by genomic imprinting, and only the paternal necdin gene is expressed in virtually all postmitotic neurons. Necdin forms a complex with the homeodomain protein Dlx2 to enhance its transcriptional activity. Dlx2 plays a major role in controlling tangential migration of GABAergic interneurons from the basal forebrain to the neocortex. Here, we examined whether Dlx2-expressing interneurons migrate properly in vivo in mutant mice lacking the paternal necdin gene. In necdin-deficient mice at birth, the population of Dlx2-expressing cells significantly decreased in the neocortex but increased in the preoptic area. DiI-labeled cell migration assay using organotypic forebrain slice cultures revealed that the number of cells migrating from the medial ganglionic eminence into the neocortex was significantly reduced in necdin-deficient embryos. Furthermore, necdin-deficient mice had a decreased population of neocortical GABA-containing neurons and were highly susceptible to pentylenetetrazole-induced seizures. These results suggest that necdin promotes tangential migration of neocortical GABAergic interneurons during mammalian forebrain development.
Kuwajima
Takaaki
T
Laboratory of Regulation of Neuronal Development, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
Hasegawa
Koichi
K
Yoshikawa
Kazuaki
K
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D019143:Evolution, Molecular; D005260:Female; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D009924:Organ Culture Techniques; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C069766:necdin