Sall4 regulates neuromesodermal progenitors through promoting mesodermal and restricting neural differentiation

Bi-potential neuromesodermal progenitors (NMPs) produce both neural and paraxial mesodermal progenitors in the trunk during vertebrate body elongation. We show that Sall4, a zinc finger transcription factor gene, has multiple roles in the maintenance and neural vs mesodermal differentiation balance of NMPs, as well as differentiation of their descendants. Sall4 deletion using TCre caused body/tail truncation, reminiscent of early depletion of NMPs. Analysis of the posterior tissue of mutant embryos identified expanded neural and reduced mesodermal tissues, demonstrating a role of Sall4 in the NMP differentiation balance. Moreover, Sall4 regulates differentiation of both mesodermal and neural progenitors. Genes regulating presomitic mesoderm differentiation are downregulated in Sall4 mutants. In the neural compartment, gene/protein expression analysis provides evidence that differentiation of NMP towards post-mitotic neuron is accelerated in Sall4 mutants. Taken together, our data provide evidence that Sall4 is a regulator of NMPs and differentiation of their progenies in mouse embryos.