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Peer-reviewedCC BY 4.0EMBO Reports

BBX maintains mammalian brain development by repressing p53-mediated p21 expression

  • Youngik Yoon1
  • Gwang Yeong Kim1
  • Woo Young Lim1
  • Saeah Hwang1
  • Solji Lee1
  • Dongrok Yoon2
  • Samuel J Pleasure3
  • Keejung Yoon1,2
  1. 1Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, South Korea
  2. 2Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, South Korea
  3. 3Department of Neurology, University of California San Francisco, San Francisco, CA USA
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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.

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Cite

BibTeXRIS
BibTeX
@article{yoon2026maintains,
  title = {{BBX maintains mammalian brain development by repressing p53-mediated p21 expression}},
  author = {Youngik Yoon and Gwang Yeong Kim and Woo Young Lim and Saeah Hwang and Solji Lee and Dongrok Yoon and Samuel J Pleasure and Keejung Yoon},
  journal = {EMBO Reports},
  year = {2026},
  month = sep,
  doi = {10.1038/s44319-026-00949-4},
  url = {https://doi.org/10.1038/s44319-026-00949-4},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - BBX maintains mammalian brain development by repressing p53-mediated p21 expression
AU  - Youngik Yoon
AU  - Gwang Yeong Kim
AU  - Woo Young Lim
AU  - Saeah Hwang
AU  - Solji Lee
AU  - Dongrok Yoon
AU  - Samuel J Pleasure
AU  - Keejung Yoon
PY  - 2026
DA  - 2026/09/25
JO  - EMBO Reports
DO  - 10.1038/s44319-026-00949-4
UR  - https://doi.org/10.1038/s44319-026-00949-4
AB  - 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.
SN  - 1469-221X
SN  - 1469-3178
ER  -