Table 1.

Comparison of findings on Gpr124, Reck, and their functional relationship in different experimental systems

	In vivo				In vitro
	Mouse		Zebrafish		HEK‐293 cells
	Phenotype		Phenotype		TOP‐flash assay
	Gpr124 KO	Reck cKO (Tie2) *cKO (Reck‐CreERT2)	gpr124 KO	reck MO/†KO	Gpr124, Reck, Fzd, Lrp, Wnt7a/b
Brain vasculature	‐ CNS hemorrhage ‐ Glomeruolid malformation ‐ PNVP thickening ‐ Avascular telencephalon	‐ Cranial hemorrage ‐ Dilated vessels	Avascular brain	‐ Avascular brain
BBB	‐ Low Glut‐1 expression ‐ Breakdown (tracer; Cullen)	?	?	?
DRG	?	?	Absent	Absent, cell‐autonomous† (Prendargast)
Endothelial cells	Failure in chemotactic migration and sprouting in vitro (Cdc42‐dependent, VEGF‐independent, cell‐autonomous)	Tip cells mislocalized in aortic ring assay (Fig. 3)*	‐ Lack of vascular sprouting into the hindbrain tissue ‐ Loss of tip‐cell sprouts from PHBC (cell autonomous)	‐ Lack of vascular sprouting into the hindbrain tissue (non cell‐autonomous) ‐ PHBP hyperplasia (Ulrich)†
Mural cells	?	Mislocalized in vivo and in aortic ring assay (Fig. 3)*	No change	No change
Wnt signaling	Reduced	?	Reduced	Reduced	Ligand (Wnt7a/b)‐specific enhancement of canonical Wnt signaling by Gpr124 plus Reck
Timing of death	E15‐before adulthood	E15‐P0	~50% healthy and fertile	Before day 12†
Other findings	Tg (Tie2) mice: brain hypervascularity	‐ Defects in cortical development ‐ Reck KO: lethal around E10.5 with abdominal hemorrhage	‐ Smaller body size ‐ Disrupted skin pigmentation pattern		‐ Co‐localization of Gpr124 and Reck (PLA; Vanhollebeke) ‐ Gpr124 interacts with DLG1 (Posokhova)
References	Kuhner, Anderson, Cullen, Zhou, Posokhova	Almeida*, Oh, Chandana	Vanhollebeke	Vanhollebeke, Ulrich†, Prendargast†	Vanhollebeke, Zhou, Posokhova

KO, global knockout; cKO, conditional or cell type‐specific knockout; MO, morpholino‐mediated knockdown; Tie2, endothelial cell‐specific promoter; PNVP, perineural vascular plexus; Tg, transgenic; PLA, proximity ligation assay. *Results with Reck cKO mice; †Results with reck KO fish.