Ventral body wall (VBW) defects are among the most common congenital malformations, yet their embryonic origin and underlying molecular mechanisms have remained poorly characterized. Although transforming growth factor beta (TGF-β) signalling is essential for VBW closure the responding cells are not known. Here we identify a population of migratory myofibroblasts at the leading edge of the closing VBW that express the actin-binding protein Transgelin (TAGLN) and TGF-β receptor (TGFβR). These cells respond to a temporally regulated TGF-β2 gradient originating from the epithelium of the primary body wall. Targeted elimination of TGFβR2 in TAGLN+ cells impairs midline closure and prevents the correct subsequent patterning of the musculature and skeletal components. Remarkably, deletion of TGFβR2 in myogenic or chondrogenic progenitor cells does not manifest in midline defects. Our results thus indicate a pivotal significance of VBW myofibroblast in orchestrating ventral midline closure by mediating the response to TGF-β gradient. Altogether, our data enables us to distinguish a highly regulated epithelial-mesenchymal signalling and successive cellular migration events in VBW closure that explain early morphological changes underlying the development of congenital VBW defects.