The vertebrate gastro-intestinal (GI) tract consists of a regionalized epithelial tube surrounded by mesenchyme that later differentiates into smooth muscle. During the early stages of stomach patterning in chick embryos, the primitive GI track is colonized by vagal enteric neural crest cells (vENCCs), which will give rise to the enteric nervous system (ENS). The important role of the ENS in controlling GI function is well understood, but its contribution to the development of the GI tract has never been addressed. On p. 331, Sandrine Faure, Pascal de Santa Barbara and co-workers demonstrate that vENCC ablation impairs mesenchyme proliferation and differentiation. Moreover, reducing the number of vENCCs alters the molecular identity of both the mesenchyme and the epithelium, such that they express intestinal markers. Mechanistically, the authors show that these defects in stomach patterning and differentiation result from the ectopic activation of Notch and BMP4 signalling; the downregulation of both these pathways is necessary for proper stomach development. Altogether, this work reveals that vENCCs control stomach patterning and differentiation through the inhibition of Notch, shedding light onto the mechanisms that govern the contribution of the ENS to GI tract development.