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Radial Glial Neural Progenitors Regulate Nascent Brain Vascular Network Stabilization Via Inhibition of Wnt Signaling

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Ablation of neural progenitors results in defective cortical angiogenesis.

(A–B) Neonatal brain hemorrhage in orc3 mutants. Immunoglobulin reactivity further confirmed patterns of hemorrhage (B). (C–F) Vessel morphology at P0 along the anterior-posterior axis. IB4 (in green) and laminin (LN, in red) staining revealed severe loss of vessels in mutants in both the anterior (C and D) and posterior (E and F) cortex. (G–H) Quantitative analysis of cortical plate vessel density and branching frequency. Dramatic reductions in both vessel density (G) and branch point frequency (H) were observed (p = 1.76×10−14 and p = 1.01×10−8, respectively; n = 9). (I–J) Correlation between radial glial density and vessel density (I) as well as between radial glial density and vessel branching frequency (J) in the medial cortex of control, orc3/nestin-cre, and orc3/hGFAP-cre mutant neonates. The correlation coefficient was 0.97 for the former (I) and 0.98 for the latter (J). Scale bar (in F): 500 µm for (B–F).

Figure 3

doi: https://doi.org/10.1371/journal.pbio.1001469.g003