Poster Presentation ANZSCDB National Scientific Meeting 2019

Revealing the function of Nr6a1 in axial elongation and body size determination (#Poster 11)

Yi-Cheng Chang 1 , Jan Manent 1 , Siew Fen Lisa Wong 1 , Gabriel Hauswirth 1 , Edwina McGlinn 1
  1. EMBL Australia, Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia

Vertebrates display great diversity in their body axial formulae, both in the number of vertebral elements and in their regional identity. The primary body axis elongates progressively, by adding new tissues from the posterior end, driven and supplied by a population of axial progenitors located in the posterior growth zone known as the neuromesodermal progenitor (NMP). Recent studies from our lab have shown that two key factors controlling the trunk-to-tail transition, Gdf11 and microRNA-196 (miR-196), act synergistically to regulate the total number of vertebral elements in the mouse embryo. However, the cellular and molecular mechanisms acting downstream of these key factors are not well characterised. Here, we propose Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a critical regulator controlling the number of trunk vertebral elements. We show that across amniote embryos, Nr6a1 is highly expressed in the posterior growth zone during early axial elongation, with expression cleared from this zone at the trunk-to-tail transition. At this site, we find that the expression level of Nr6a1 positively correlates with the number of trunk elements, when comparing wildtype and genetically modified mice that harbour additional trunk vertebrae. Moreover, in vivo maintenance of Nr6a1 activity during the trunk-to-tail transition is able to expand the trunk region in mouse by 3-6 elements. Parallel in vitro studies indicate that Nr6a1 activity is essential for correct Hox cluster expression and impacts the choice between neural and mesodermal fate within the NMP.  Collectivley, this work identifies Nr6a1 as an important developmental regulator required for correct formation and patterning of the primary body axis.