Tbx3 regulates cell fate decisions during murine endodermal and pancreatic development

Tbx3 is a member of the T-box family of transcription factors, which are known to play key roles in early embryonic development. Moreover, mutations within Tbx3 and some of its closely related family members give rise to several human developmental syndromes and misexpression of these genes have been implicated in several types of cancers, including colon cancer. However, the mechanisms by which Tbx3 and related family members contribute to diseases remain poorly understood. Interestingly, Tbx3 null mice die around E12.5 due to cardiac and york sack defects. Up to now, the pancreas of those mice has never been characterized. We identified that Tbx3 strongly promotes lineage commitment towards an endodermal cell fate and upon overexpression of Tbx3, we could enhance the number of Pdx1 expressing cells. In addition, Tbx3 null mice were analysed over time of pancreatic development. Moreover, we identified that Tbx3 directly activates a Nodal signalling cascade and, given the recently identified role of Nodal signalling within pancreatic cancer, our study provides an important bridge for understanding the relationship between Tbx3 in early development and a potential role in oncogenic processes.