Co-expression of Tbx6 and Sox2 identifies a novel transient neuromesoderm progenitor cell state [RESEARCH REPORT]

Alok Javali, Aritra Misra, Karolis Leonavicius, Debalina Acharya, Bhakti Vyas, and Ramkumar Sambasivan

The elongation of body axis during development is a key aspect of body plan. Bi-potential neuromesoderm progenitors (NMPs) ensure the axial growth of embryos by contributing both to the spinal cord and mesoderm. The current model for the mechanism controlling NMP deployment invokes Tbx6, a T-box factor, to drive mesoderm differentiation of NMPs. Here, we identify a new population of Tbx6+ cells in a subdomain of NMP niche in mouse embryos. Based on co-expression of a progenitor marker Sox2, we identify this population to represent a transient cell state in the mesoderm-fated NMP lineage. Genetic lineage tracing confirms the presence of Tbx6+ NMP cell state. Furthermore, we report a novel aspect of documented Tbx6 mutant phenotype, i.e., an increase from two to four ectopic neural tubes, corresponding to the switch in NMP niche, highlighting the importance of Tbx6 function in NMP fate decision. This study emphasizes the function of Tbx6 as the bi-stable switch turning mesoderm fate "on" and progenitor state "off", and thus, has implications for the molecular mechanism driving NMP fate choice.

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