Fig. 1

Knl1 conditional deletion from cortical NPCs led to microcephaly and NPC loss. a Dorsal view of Knl1+l+;hGFAP-Cre and Knl1fl/fl;hGFAP-Cre (cKO) P4 brain. Cortical area was significantly reduced in cKO compared to littermate control (ctrl) (mean, two-tailed unpaired t-test, ctrl: n = 4, cKO: n = 3 animals, scale bar: 1 mm). b DAPI staining in coronal section of Knl1+l+;hGFAP-Cre and Knl1fl/fl;hGFAP-Cre (cKO) P4 brain. Cortical plate (CP) thickness was significantly reduced in cKO compared to ctrl (mean, two-tailed unpaired t-test, ctrl: n = 7, cKO: n = 4 animals, scale bar: 500 µm). c Postnatal survival analysis showed reduced survival in cKO (n = 11) compared to ctrl (n = 25 animals). d Cortical layer marker analysis at P4 revealed no significant change in BCL11B+ (L5, magenta) or TBR1+ (L6, red) neurons but a significant reduction in number of CUX1+ (L2–4, green) and POU3F2+ (L2–5, cyan) neurons in cKO compared to ctrl (mean, two-tailed unpaired t-test, TBR1, ctrl: n = 3, cKO: n = 4, BCL11B, ctrl: n = 6, cKO: n = 4, POU3F2, ctrl: n = 3, cKO: n = 3, CUX1, ctrl: n = 6, cKO: n = 4 animals, scale bar: 100 µm). e NPC marker analysis of E13.5 cortex revealed no significant change in cKO. At E15.5 and E16.5, SOX2+ apical progenitors (APs, green) and EOMES+ intermediate progenitors (IPs, magenta) were significantly reduced in number in cKO (mean, two-tailed unpaired t-test, EOMES E13.5, ctrl: n = 3 cKO: n = 5, E15.5, ctrl: n = 4, cKO: n = 4, E16.5, ctrl: n = 3, cKO: n = 3, SOX2 E13.5, ctrl: n = 3, cKO: n = 5, E15.5, ctrl: n = 3, cKO: n = 3, E16.5, ctrl: n = 3, cKO: n = 3 animals, scale bar: 50 µm). Aberrant gaps in immunolabeling (arrowheads) were observed in cKO. MB midbrain, CPu caudate putamen, IZ intermediate zone