Epithelial tissues are fundamental to the structural and functional organization of multicellular organisms, guiding morphogenesis during development and preserving tissue homeostasis. During early embryonic development, particularly around implantation, the epiblast undergoes a significant reshaping from an unorganized cluster of embryonic stem cells (ESCs) to an apical-basal polarized epithelial tissue, which further encloses the proamniotic cavity. However, the precise molecular and/or biophysical mechanisms underlying these intricate cellular transitions, including actomyosin reorganization, relocation of adherent junctions, cell fate specification and the formation of the proamniotic cavity, remain elusive. Deciphering the coordination of these complex behaviors during epithelial tissue morphogenesis represents a substantial challenge in developmental biology. Here, we uncover a previously unexpected role for Netrin-1 signaling via its receptors Neo1 and Unc5b in coordinating epithelial polarization and lumen formation. Using CRISPR/Cas9 knockout ESCs in 3D self-organization models, we observed that loss of either receptor impairs proper localization of adherens junctions (E-Cadherin), disrupts actomyosin network organization, and leads to failed lumenogenesis. Notably, we identify intracellular calcium release as a critical downstream event of Netrin-1 signaling. This calcium wave activates calmodulin and CaMKII which have previously been implicated in actin remodeling in neuronal systems. These findings support the idea that calcium signaling could contribute to the coordination of cytoskeletal dynamics and junctional organization during early epithelial development. While further investigation is needed to fully understand these pathways, a deeper understanding of these processes may also provide insights into epithelial behaviors reactivated in pathological contexts such as cancer.