Tbx3 directs cell fate decision toward mesendoderm
InstitutionsUKU. Klinik für Innere Medizin I
Institut für Anatomie und Zellbiologie
Pluripotency and cell fate decisions are dependent on networks of key transcriptional regulators. Previous reports demonstrated additional features of pluripotency-associated factors during early lineage specification. The T-box transcription factor Tbx3 has been suggested in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show the dynamic expression of Tbx3 during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Notably, forced Tbx3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/SMAD2 signalling. Tbx3 loss-of-function analyses performed in Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between Tbx3 and Tbx2 during Xenopus gastrulation. In summary, we define additional facets of Tbx3 actions and map Tbx3 as an upstream regulator of the mesendoderm transcriptional specification program during gastrulation.
Subject HeadingsZellklon [GND]
Cell lineage [MeSH]
Pluripotent stem cells [MeSH]