Kawaguchi, D. | bioRxiv Science

bioRxiv2024

Embryonic diversification of adult neural stem cells and ependymal cells

Both adult neural stem (type B) cells and ependymal (type E) cells in the mouse ventricular-subventricular zone (V-SVZ) are derived from slowly dividing (or quiescent) embryonic neural stem-progenitor cells (NPCs) that are set aside during development. However, it has remained unclear whether fate diversification between adult type B and type E cells actually occurs during embryogenesis. Here we performed single-cell transcriptomic analysis of slowly dividing embryonic NPCs and identified cell subpopulations transcriptionally similar to adult type B or type E cells. The type B- like embryonic cells appeared to emerge before embryonic day (E) 13.5, whereas the type E-like cells became evident between E13.5 and E16.5. Genes differentially expressed in B-like embryonic cells (versus E-like cells) included Tmem100, Cadm2, and bone morphogenetic protein (BMP)-induced genes. Forced expression of an active form of BMP receptor (ALK2QD), TMEM100, or CADM2 in embryonic NPCs resulted in preferential generation of adult type B cells relative to type E cells in the postnatal brain. Moreover, knockdown of TMEM100 resulted in relative enrichment of type E cells over type B cells. Our results indicate that the embryonic origin of adult type B cells and that of type E cells have already diverged molecularly during embryogenesis, and they have identified key molecular players in this fate bifurcation.

developmental biology↗

bioRxiv2019

Role of the imprinted allele of the p57Kip2 gene in mouse neocortical development

Imprinted genes are expressed from only one allele in a parent of origin-specific manner. The cyclin-dependent kinase inhibitor p57Kip2 (p57) is encoded by an imprinted gene, with the paternal allele being silenced. The possible expression and function of the paternal allele of p57 have remained little studied, however. We now show that the paternal allele of the p57 gene is expressed at a low level in the developing mouse neocortex. Surprisingly, the central nervous system-specific conditional deletion of the paternal allele (pat cKO) at the p57 locus resulted in a marked reduction in brain size. Furthermore, pat cKO gradually reduced the number of neural stem-progenitor cells (NPCs) during neocortical development, and thus reduced the number of upper-layer neurons, which were derived from late-stage NPCs. Our results thus show that the paternal allele of the p57 locus plays a key role in maintenance of NPCs during neocortical development.

developmental biology↗