biostudies-literatureUnknownDhanya SKDST-SERB Start Iup research grantDBT-MK Bhan Young Researcher FellowshipDBT-inStem Core fundsDBT/Wellcome Trust India AllianceWellcome TrustDBT Har Gobind Khorana Innovative Young Biologist FellowshipDBT/Wellcome Trust India Alliance:Intermediate Career FellowshipPratiksha Grant to inStemChromatin regulation plays a crucial role in neocortical neurogenesis, and mutations in chromatin modifiers are linked to neurodevelopmental disorders. RBBP4 is a core subunit of several chromatin-modifying complexes; however, its functional role and genome-wide occupancy profile in the neocortical primordium are unknown. To address this, we performed RBBP4 knockdown using CRISPR/Cas9 on neocortical progenitors derived from mice of both sexes at embryonic age 12.5 during deep-layer neurogenesis. Our study demonstrates that downregulation of RBBP4 in the E12.5 neocortical progenitors reduced neuronal output, specifically affecting CTIP2-expressing neurons. We demonstrate that RBBP4 plays an essential role in regulating neocortical progenitor proliferation. However, overexpression of RBBP4 aeNeuroENEURO.0391-23.2024https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617683biostudies-literatureHistone-binding protein RBBP4 is necessary to promote neurogenesis in the developing mouse neocortical progenitors.PMC7617683BT/13/IYBA/2020/02SRG/2020/001612IA/I/19/1/504288HRD-12/4/2020-AFS-DBT-13815Dhanya SKMohanty SSwathi KSKalia KAzam TMuralidharan BD'Souza LChannakkar ASReddy PCfalseHistone-binding protein RBBP4 is necessary to promote neurogenesis in the developing mouse neocortical progenitors.Chromatin regulation plays a crucial role in neocortical neurogenesis, and mutations in chromatin modifiers are linked to neurodevelopmental disorders. RBBP4 is a core subunit of several chromatin-modifying complexes; however, its functional role and genome-wide occupancy profile in the neocortical primordium are unknown. To address this, we performed RBBP4 knockdown using CRISPR/Cas9 on neocortical progenitors derived from mice of both sexes at embryonic age 12.5 during deep-layer neurogenesis. Our study demonstrates that downregulation of RBBP4 in the E12.5 neocortical progenitors reduced neuronal output, specifically affecting CTIP2-expressing neurons. We demonstrate that RBBP4 plays an essential role in regulating neocortical progenitor proliferation. However, overexpression of RBBP4 a2024-01-01T00:00:00Z2024 Nov2026-04-18T03:21:02.822Z2026-04-18T03:11:37.303ZS-EPMC76176833959222710.1523/ENEURO.0391-23.2024