miR-151-5p Regulates Neural Stem Cell Fate by Targeting Aph1a to Modulate Notch Signaling Gradients

Conditional knockout of miR-151-5p led to increased Sox2 expression and enhanced NSC proliferation. Mechanistically, Aph1a, a core subunit of the γ-secretase complex, was identified as a direct target of miR-151-5p.

Overexpression of Aph1a phenocopied the knockout phenotype, promoting NSC proliferation via elevated NICD levels. Our results demonstrate that miR-151-5p biases NSC fate specification by targeting Aph1a to modulate Notch signaling, thereby fine-tuning the balance between NSC maintenance and differentiation. This study reveals a novel miR-151-5p/Aph1a/Notch signaling axis governing NSC fate, providing a critical post-transcriptional regulatory layer in mammalian neocortical development.