Molecular mechanisms of Gdf11/Tgfbr1 activity regulating the trunk to tail transition and development of posterior appendages.

Signaling pathways regulate multiple aspects of vertebrate embryonic development. Members of Transforming Growth Factor β (Tgfβ) superfamily in particular, are involved in embryogenesis starting from the earliest cell-fate decisions and including establishment and patterning of the main body axis and its appendages. One of Tgfβ family ligands, Growth differentiation factor 11 (Gdf11), is an evolutionary conserved regulator of vertebrate trunk length due to its function as inductor of the trunk to tail transition. In the context of trunk to tail transition Gdf11 activities are mediated by the Tgfbr1 type I receptor: its premature activation in axial progenitors region is sufficient to induce the transition more anteriorly

A Tgfbr1/Snai1-dependent developmental module at the core of vertebrate axial elongation

LISBOA-01?0145-FEDER-030254 SCML-MC-60-2014 LISBOA-01-0145-FEDER-022170 PD/BD/128426/2017 PD/BD/128437/2017 MR/S008799/1 MR/ K011200/1 DEV-170806Formation of the vertebrate postcranial body axis follows two sequential but distinct phases. The first phase generates pre-sacral structures (the so-called primary body) through the activity of the primitive streak on axial progenitors within the epiblast. The embryo then switches to generate the secondary body (post-sacral structures), which depends on axial progenitors in the tail bud. Here we show that the mammalian tail bud is generated through an independent functional developmental module, concurrent but functionally different from that generating the primary body. This module is triggered by convergent Tgfbr1 and Snai1 activities that promote an incomplete epithelial to mesenchymal transition on a subset of epiblast axial progenitors. This EMT is functionally different from that coordinated by the primitive streak, as it does not lead to mesodermal differentiation but brings axial progenitors into a transitory state, keeping their progenitor activity to drive further axial body extension.publishersversionpublishe