BBX, p53 aracılığıyla p21 ifadesini baskılayarak memeli beyin gelişimini sürdürür

Özet (abstract)

Brain development requires coordinated regulation of neural stem cell (NSC) proliferation, differentiation, and neuronal migration. Here, we identify bobby sox homolog (BBX), a nuclear HMG box domain-containing protein enriched in mouse embryonic cortical germinal zones, as a regulator of corticogenesis. In the embryonic cortex, BBX depletion reduces SOX2-expressing NSCs, promotes premature cell-cycle exit, disrupts cortical cell positioning, causes abnormal clustering of newborn neurons, and impairs migratory neuron morphology. RNA-seq and public ChIP-seq analyses, together with biochemical assays, show that BBX interacts with p53 and suppresses p53-dependent p21 expression. Consistent with activation of the p21 pathway, BBX knockdown increases premature cell-cycle exit and senescence-associated features, including γH2AX accumulation and senescence-associated gene expression. Co-depletion of p21 rescues BBX knockdown-induced defects in NSC maintenance, neuronal distribution, and morphology. In line with this, depletion of retinoblastoma protein (RB), a major mediator of p21-dependent senescence, restores abnormal cortical cell distribution. These findings indicate that BBX maintains normal cortical development by restraining the p53-p21-RB axis, thereby preventing premature cell-cycle exit and senescence in developing neural cells.

Yazarların özeti; kaynağından alınmıştır. EMBO Reports, 2026 · DOI ↗