{'fraction_non_alphanumeric': 0.03475513428120063, 'fraction_numerical': 0.020537124802527645, 'mean_word_length': 5.633507853403142, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
VEGF‐A mediates collateral formation during embryogenesis

The density of native (pre‐existing) is a key determinant of the severity of tissue damage after vascular obstruction. We previously showed that VEGF expression influences native collateral density in the murine brain and hindlimb. When collaterals form and how VEGF influences the process is not understood. Here we examined collateral formation in the cerebral pial circulation of mouse embryos. Collaterals emerged at embryonic day (E) 14.5 as late‐forming EphrinB2‐positive sprouts between existing arterial trees that were superficial to pial capillaries and veins. Density was higher in VEGF‐hi (overexpressing) and lower in VEGF‐lo (underexpressing) mice compared to wildtypes (WT) at all embryonic stages. Expression of other angiogenesis‐related genes was similar in the collateral zone of E14.5 VEGF‐hi and –lo embryos. However, conditional global and/or endothelial specific knockdown of VEGF, VEGFR2 and Notch cleavage between E12.5 and E14.5 significantly altered collateral density compared to WT littermates. Thus, paracrine, not autocrine, VEGF signaling via VEGFR2 and the Notch pathway specifically between E12.5‐E14.5 is an important determinant of collateral formation. (NIH‐HL90655 JEF)