Smith lab Developmental Biology Laboratory
: The roles of T-box transcription factors in mesoderm formation and early development
Introduction
The induction of mesoderm is among the earliest cell fate decisions occurring in bilaterian embryos as a consequence of zygotic genome activation and TGF-b signalling.
This event leads into gastrulation, a period of complex tissue rearrangements (morphogenetic movements) segregating mesoderm from neural and endodermal tissue.
On a genetic level nascent mesoderm correlates with the activation of several T-box transcription factors such as Eomesodermin and Brachyury. In fact, these T-box transcription factors are essential for the maintenance of mesodermal cells and their derivatives. Without these transcriptional inputs cells in anatomical positions of mesoderm switch to a neural fate at least in part due to their common cell lineage.
Consequently, such embryos develop an excess of neural tissue at the expense of mesoderm. We are making use of classic embryological and state of the art technologies to dissect in vivo how naïve cells adopt these different cell fates to complete a well-formed vertebrate embryo.
Figure 1: Xenopus Brachyury (Xbra) marks precursor cells giving rise to mesoderm and neural tissues. Xbra is a sequence-specific transcription factor recognising a 9-bp motif. This binding motif was determined de novo from Xbra binding profiles at gastrula stage (ChIP-Seq) and confirmed in vitro by Surface Plasmon Resonance (SPR). Morpholino-mediated knockdown experiments revealed functional redundancy between Brachyury paralogues Xbra and Xbra3 in regulating axis elongation.
