Greb1is required for axial elongation and segmentation in vertebrate embryos

Abstract

During vertebrate embryonic development, the formation of axial structures is driven by a population of stem-like cells that reside in a region of the tailbud called the chordoneural hinge (CNH). We have compared the CNH transcriptome with those of surrounding tissues and shown that the CNH and tailbud mesoderm are transcriptionally similar, and distinct from the presomitic mesoderm. Amongst CNH-enriched genes are several that are required for axial elongation, including Wnt3a, Cdx2, Brachyury/T and Fgf8, and androgen/estrogen receptor nuclear signalling components such as Greb1.We show that the pattern and duration of tailbud Greb1 expression is conserved in mouse, zebrafish, and chicken embryos, and that Greb1 is required for axial elongation and somitogenesis in zebrafish embryos. The axial truncation phenotype of Greb1 morphant embryos is explained by much reduced expression of No tail (Ntl/Brachyury) which is required for axial progenitor maintenance. Posterior segmentation defects in the morphants (including misexpression of genes such as mespb, myoD and papC) appear to result, in part, from lost expression of the segmentation clock gene, her7. Brown, J. M. and Storey, K. G. (2000). A region of the vertebrate neural plate in which neighbouring cells can adopt neural or epidermal fates. Current biology : CB 10, 869-872. Cambray, N. and Wilson, V. (2002). Axial progenitors with extensive potency are localised to the mouse chordoneural hinge. Development 129, 4855-4866. Cambray, N. and Wilson, V. (2007). Two distinct sources for a population of maturing axial progenitors. Development 134, 2829-2840. Catala, M., Teillet, M. A., De Robertis, E. M. and Le Douarin, M. L. (1996). A spinal cord fate map in the avian embryo: while regressing, Hensen's node lays down the notochord and floor plate thus joining the spinal cord lateral walls. Development 122, 2599-2610. Choorapoikayil, S., Willems, B., Strohle, P. and Gajewski, M. (2012). Analysis of her1 and her7 mutants reveals a spatio temporal separation of the somite clock module. PloS one 7, e39073. Deniziak, M., Thisse, C., Rederstorff, M., Hindelang, C., Thisse, B. and Lescure, A. (2007). Loss of selenoprotein N function causes disruption of muscle architecture in the zebrafish embryo. Exp Cell Res 313, 156-167.