During development, neuromesodermal (NM) stem cells give rise to both neural cells and paraxial presomitic mesoderm (PSM) cells, but what dictates PSM fate? Here, Terry Yamaguchi and colleagues show that a single transcription factor – mesogenin 1 (Msgn1) – acts as a master regulator of PSM development (p. 4285). They show that the overexpression of Msgn1 in mouse ESCs cultured as embryoid bodies (EBs) is sufficient to drive PSM differentiation. Microarray and ChIP-seq analyses of Msgn1-overexpressing EBs confirm that Msgn1 controls the expression of key regulators of PSM development, including those involved in epithelial-mesenchymal transition and segmentation. Importantly, the researchers demonstrate that Msgn1 overexpression in NM stem cells in vivo biases fate towards the PSM; the contribution of these cells to the neural tube is reduced while the number of PSM cells is dramatically increased. Finally, the authors show that Msgn1 overexpression can partly rescue the PSM differentiation defects observed in Wnt3a−/− embryos, suggesting that Msgn1 functions downstream of Wnt3a as master regulator of PSM fate. Given the role of the PSM as a precursor for a multitude of cell types, this finding has important implications for the fields of cellular reprogramming and regenerative medicine.