Posphorylation-Dependent Activation of Transcription Factors Drives Cell Fate Switching in Cortical Development

Here, we show that phosphorylation of TFs is a key mechanism driving cell fate transitions during neurogenesis and gliogenesis. Using multi-omics profiling of embryonic mouse cortex, we identify stage-specific phosphorylation of Hmgn3 and Nfib as critical for neuronal differentiation and maturation.

Phospho-mutant analyses reveal impaired migration and astrocyte differentiation. CUT&RUN and scATAC-seq integration show phosphorylation-dependent enhancer binding by Nfib. Additionally, Hmgn3 and Nfib regulate distinct signaling pathways mediating cell-cell communication.