Aberrations in blood vessel diameters can disrupt hierarchical vascular patterning and cause severe congenital vascular anomalies, like arteriovenous malformations (AVMs) and venous malformations (VMs). However, despite the plethora of knowledge on the signaling pathways (Endoglin, ALK1, SMAD4, PIK3CA, TIE2) involved in AVM and VM pathology, we still lack an understanding of the early embryonic events regulating vessel hierarchy and arteriovenous shunt formation in vivo.My findings reveal that the artery consistently responds to changes in blood flow and is dependent on flow increase for expansion of its diameter and EC size; while the vein shows context-dependent responses, with one region lacking observable changes, while another responding to an increase or decrease in flow similar to the artery, but to a lesser extent. To unravel the mechanisms underlying the reduced response of vein to flow, I studied zebrafish embryos mutant for endoglin and alk1, genes with differential expression patterns in the artery and vein and whose loss of function results in AVMs. Interestingly, I discovered that both Endoglin and Alk1 were required in the vein to restrict EC size and thus limit venous diameter increases in response to flow. Conversely, utilizing a novel zebrafish pik3ca GOF mutant, I revealed that PI3K signaling promotes EC number increases in the vein. My findings support a model wherein Endoglin and Alk1 render veins less responsive to flow and thus might protect against AVMs during early development. Moreover, my data also reveals the requirement for a balance between Endoglin/Alk1 signaling and PI3K signaling to maintain proper venous diameters through a nuanced regulation of EC size and number. This study thus offers novel insights into the spatiotemporal regulation of vessel hierarchy during early development and highlights the cellular and molecular mechanisms underlying vessel-specific initiation of AVMs in vertebrate models of vascular malformations.