Insulinoma-associated 1 promotes neurogenic proliferation of cortical basal progenitors but is largely dispensable for projection neuron production

Basal progenitors (BPs) are essential contributors to mammalian cortical neurogenesis, yet the mechanisms governing their behavior remain incompletely understood. Insulinoma-associated 1 (INSM1), a SNAG-domain zinc-finger transcription factor, has been proposed to promote BP generation and expansion, although prior conclusions relied heavily on gain-of-function approaches and were limited by early lethality of Insm1 -null embryos. Here, using conditional genetic ablation of Insm1 in mouse cortical progenitors, we reveal that INSM1 is largely dispensable for BP generation but is essential for proper BP cell-cycle progression. INSM1-deficient BPs exhibit impaired S-phase entry, reduced RB phosphorylation, and downregulation of cell-cycle–related gene programs. Although neurogenesis by BPs is diminished, apical progenitors (APs) compensate by increasing symmetric amplifying divisions, expanding the AP pool and preserving production of later-born, upper-layer neurons despite reduced early-born, deep-layer neurons. These findings identify INSM1 as a critical regulator of BP neurogenic proliferation and highlight compensatory flexibility within the cortical progenitor hierarchy.