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

Abstract

Formation 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.

Diverse Routes toward Early Somites in the Mouse Embryo

“…Expression of NMP markers over time confirms the known NMP signature, with expression of T , Sox2 , Nkx1-2 , and Cdx2 at E7.5 being maintained up to E8.5. In this trajectory, the persistence of Cdh1 expression throughout upregulation of Cdh2 between E7.0 and E8.25 is consistent with an “incomplete” EMT in NMPs ( Dias et al., 2020 ). Inspection of additional EMT genes, including Epcam (epithelial marker) and Vim (mesenchymal marker), reinforced this notion, with co-expression detected in half of the predicted NMP ancestors between E7.5 and E8.0 ( Figures S2 B–S2D).…”

Rostrocaudal patterning and neural crest differentiation of human pre-neural spinal cord progenitors in vitro

“…Specifically, our data indicates that ALK4, ALK5 and ALK7 inhibition by SB431542 is acting to prevent GDF11 signalling and is sufficient to promote PNP identity and viability in our culture by maintaining LIN28A expression (Andersson et al, 2006). This is in line with recent in vivo evidence describing the involvement of TGFBR1/GDF11 in secondary neurulation (Dias et al, 2020, Aires et al, 2019).…”

Cell-to-cell heterogeneity in Sox2 and Brachyury expression ratios guides progenitor destiny by controlling their motility.

“…Biasing progenitors with mesenchymal properties towards a neural state is therefore much more likely to give a difference in motility than a change towards another mesodermal state. In lines with this explanation is the fact that during the course of axis elongation posterior progenitors undergo an epithelialmesenchymal transition before reaching their full potential to give rise to progeny in the NT and the PSM (12, 31,38). Therefore, it is likely that even though Sox2/Bra heterogeneity is present since stage HH5, regulation of progenitor destiny by cellular motility is mostly active after stage HH8 when the progenitors have become mesenchymal with cellular properties that are closer to PSM cells.…”

“…Live Imaging has been done using Zeiss Axio-imager type 2 (10X objective) and was described here (31). Briefly, stage 7-8 electroporated embryos were cultured under the microscope at 38 degrees under humid atmosphere.…”