Fig. 3.

Gpr124 is required for normal angiogenic sprouting and development of vasculature within the forebrain and spinal cord. Endothelial immunostaining for platelet endothelial cell adhesion molecule 1 (PECAM-1) (A–D and F–I) showed that, although a PNVP formed in the forebrain of both control Gpr124^Lz/WT (Het) embryos and Gpr124^Lz/Lz (KO) embryos (blue arrowheads in A and B), angiogenic sprouting into the ventral forebrain was evident only in Het embryos at E10.5 (yellow arrowheads in A and B). Similarly, vessel sprouting into the spinal cord (yellow arrowheads in F and G) from the PNVP (blue arrowheads in F and G) was reduced in the dorsal spinal cord and absent in the ventral spinal cord of KO embryos at E10.5. Vessels were grossly aberrant in the ventral forebrain in KO embryos at E12.5, featuring glomeruloid tuft–like endings (yellow arrowheads in D); large regions in the periventricular portion of the ganglionic eminences, and in the lateral pallium, remained avascular. A thickening of the PNVP often occurred along the lateral pallium (blue arrowheads in C and D). Abnormal vessel formations also were present in the ventral spinal cord of KO embryos at E12.5 (yellow arrowheads in I). Histochemical staining for endogenous peroxidase contained in red blood cells (E and J) clearly demonstrated accumulation of red blood cells in neural tissue surrounding abnormal vessels in both brain and ventral spinal cord as well as in the central canal (arrowheads in E and J). Sections in E and J were counterstained with eosin. VFB, ventral forebrain; MGE, medial ganglionic eminence; LGE, lateral ganglionic eminence.