Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip

• DOI: 10.1002/advs.202411732
• Publication Date: 2025-01-07T13:44:01Z
• Authors: Jiarui Wu; Haoyang Yu; Xinyi Dou; Bin Yin; Lin Hou; Yuanchao Xue; Boqin Qiang; Pengcheng Shu; Xiaozhong Peng
• Keywords: Neocortex; Cell fate determination; Conditional gene knockout; Fate mapping

Abstract The development of the mammalian neocortex is precisely regulated by temporal gene expression, yet regulatory mechanisms cortical neurogenesis, particularly how radial glial cells (RGCs) sequentially generate deep to superficial neurons, remain unclear. Here, hnRNP family member Syncrip (hnRNP Q) identified as a key modulator neuronal differentiation in neocortical neurogenesis. knockout RGCs disrupts and abnormal localization, ultimately resulting layer defects well learning memory impairments mice. Single‐cell RNA sequencing analysis demonstrated that late‐stage stalling transcriptional progression RGCs. Mechanistically, maintains transcription process‐related factors recruiting stabilization complexes through phase separation, crucially regulating Notch signaling pathway determines fate Furthermore, pathogenic human mutations weaken its phase‐separation capability, failing form stable normally. Thus, acts mediator posttranscriptional mechanisms, governing advancement intrinsic programs. This study establishes an intracellular mechanism for regulation progressive determination