Fig. 1 | Nature Communications

Fig. 1

From: Robust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Knl1 deletion

Fig. 1The alternative text for this image may have been generated using AI.

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

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