File:Chicken body elongation model.jpg

Chicken Body Elongation Model

Summary of signalling pathway interactions and cell fate changes underlying body axis elongation arrest.

At HH22 Bra is expressed in notochord, CNH, and mesodermal progenitors (overlapping with Sox2 in neural CNH) and is maintained by FGF (and Wnt) signalling, while Sox2 is confined to neural tube and neural-CNH (see Figure 1A). From this stage Raldh2 [17] and Crabp2 begin to be detected in tailbud mesoderm progenitors (signals that induce Raldh2 here remain to be determined). FGF signalling no longer inhibits Raldh2 nor represses Crabp2, and Cyp26a is downregulated; consequently, RA signalling begins to rise in the tailbud. FGF signalling is required to maintain Bra (except in proximal notochord) as well as Tbx6L and Wnt3a (not shown) in mesoderm progenitors. At HH24 FGF signalling suddenly declines, leading to loss of Bra and expansion of Sox2 expression (dashed arrow) into the previous mesoderm progenitor domain, which reflects continued cell ingression from the CNH. At this stage Crabp2 is now detected in the neural-CNH and position of the mesoderm progenitors, indicating rising retinoid signalling, which can repress FGF ligands and signalling. By HH26/27 FGF signalling is not detected and the notochord ends abruptly encircled by Sox2 expressing cells. Cell death is widespread in the tailbud and is promoted by retinoid signalling.

Reference

doi:10.1371/journal.pbio.1001415.g009

http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001415

Copyright

© 2012 Olivera-Martinez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Figure 9. Journal.pbio.1001415.g009.jpg

PLoS Biol. 2012 Oct;10(10):e1001415. doi: 10.1371/journal.pbio.1001415. Epub 2012 Oct 30. Loss of FGF-dependent mesoderm identity and rise of endogenous retinoid signalling determine cessation of body axis elongation. Olivera-Martinez I, Harada H, Halley PA, Storey KG. Source Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee, United Kingdom. Abstract The endogenous mechanism that determines vertebrate body length is unknown but must involve loss of chordo-neural-hinge (CNH)/axial stem cells and mesoderm progenitors in the tailbud. In early embryos, Fibroblast growth factor (FGF) maintains a cell pool that progressively generates the body and differentiation onset is driven by retinoid repression of FGF signalling. This raises the possibility that FGF maintains key tailbud cell populations and that rising retinoid activity underlies cessation of body axis elongation. Here we show that sudden loss of the mesodermal gene (Brachyury) from CNH and the mesoderm progenitor domain correlates with FGF signalling decline in the late chick tailbud. This is accompanied by expansion of neural gene expression and a similar change in cell fate markers is apparent in the human tailbud. Fate mapping of chick tailbud further revealed that spread of neural gene expression results from continued ingression of CNH-derived cells into the position of the mesoderm progenitor domain. Using gain and loss of function approaches in vitro and in vivo, we then show that attenuation of FGF/Erk signalling mediates this loss of Brachyury upstream of Wnt signalling, while high-level FGF maintains Brachyury and can induce ectopic CNH-like cell foci. We further demonstrate a rise in endogenous retinoid signalling in the tailbud and show that here FGF no longer opposes retinoid synthesis and activity. Furthermore, reduction of retinoid signalling at late stages elevated FGF activity and ectopically maintained mesodermal gene expression, implicating endogenous retinoid signalling in loss of mesoderm identity. Finally, axis termination is concluded by local cell death, which is reduced by blocking retinoid signalling, but involves an FGFR-independent mechanism. We propose that cessation of body elongation involves loss of FGF-dependent mesoderm identity in late stage tailbud and provide evidence that rising endogenous retinoid activity mediates this step and ultimately promotes cell death in chick tailbud. PMID 23118616