Deficiency of Pdap1 Results in Embryonic Lethality and Diminished Vascularization

Platelet-derived growth factor associated protein 1 (PDAP1) is implicated in various biological processes, including tumorigenesis and the apoptosis of mature B lymphocytes. However, its functions in organismal development and homeostasis remain poorly understood. To address this gap, we generated Pdap1 knockout mice to elucidate the physiological functions of PDAP1 in vivo. Notably, our findings indicate that the absence of Pdap1 results in early embryonic lethality by embryonic day 11.5, accompanied by a spectrum of developmental abnormalities, including growth retardation, enlarged pericardium, hemorrhage within the pericardial cavity, and impaired vascularization of the yolk sac and placental labyrinth. Analysis of PDAP1 expression during embryogenesis revealed its presence in both embryonic and extra-embryonic tissues, a spatial pattern that may underlie the vascular defects observed in the yolk sac and placenta. Comparative proteomic profiling further identified nidogen-1 (NID1) as a key PDAP1-repressed target. Mechanistically, loss-of-function and gain-of-function experiments demonstrated that NID1, at least in part, mediates PDAP1-modulated endothelial cell migration, invasion, and tube formation-critical processes in vascular morphogenesis.