Gaunt, Stephen John - University of Cambridge

研究领域

In most of the bilaterally symmetrical animals (Bilateria) the arrangement of body parts along the head-tail axis is largely specified by Hox genes. These genes are (i) usually clustered on the chromosome, at least to some extent, (ii) extensively conserved throughout the Bilateria, and (iii) expressed along the body in partially overlapping domains whose anterior boundaries are collinear with the ordering of the genes along the chromosome (the so-called collinearity rule). It is widely believed that the Hox gene cluster, the collinearity rule, and the function of Hox genes in specifying arrangement of body parts have each been inherited from the last common ancestor of the Bilateria, an animal which lived over 500 million years ago. I am interested in the functional significance of Hox gene collinearity. We recently suggested how it may have arisen in ancestral Bilaterians as a mechanism to maximise segregation between active and inactive Hox genes within the developing Hox gene cluster. This may have been to minimise erroneous spread of activity/inactivity between adjacent Hox genes. Hox proteins function as transcription factors, instructing embryonic cells on their appropriate routes of morphogenesis. Hox expression domains thus provide a genetic pre-pattern to the anatomical body plan. A central objective in developmental biology is to understand how these domains are established in the embryo. For several Hox genes, an enhancer or cis-regulatory element (CRE) in the vicinity of the gene is known to regulate the expression pattern. For mouse Hoxd11 we have shown that regulation of the CRE is mediated by Gdf11/Smad signalling. This, like several other TGFβ signalling pathways may operate as a morphogen, and may thereby specify the discreet spatial limits of Hox gene expression in the embryo. I am now extending my research to CREs of other mouse Hox genes.

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Gaunt, S. J. and Gaunt, A. L. (2016) Possible rules for the ancestral origin of Hox gene collinearity. J. Theor. Biol. 410, 1-8. Gaunt, S. J. (2015) The significance of Hox gene collinearity. Int. J. Dev. Biol. 59, 159-170. Gaunt, S. J. and Paul, Y.-L. (2014) Synergistic action in P19 pluripotential cells of retinoic acid and Wnt3a on Cdx1 enhancer elements. Int. J. Dev. Biol. 58, 307-314. Hautier, L., Charles, C., Asher, R. and Gaunt, S. J. (2014) Ossification sequence and genetic patterning in the mouse axial skeleton. J. Exp. Zool. (Mol. Dev. Evol.) 322B, 631-642. Gaunt, S. J., George, M. and Paul, Y.-L. (2013) Direct activation of a mouse Hoxd11 axial expression enhancer by Gdf11/Smad signalling. Dev. Biol. 383, 52-60. Gaunt, S. J. and Paul. Y.-L. (2012) Changes in cis-regulatory elements during morphological evolution. Biology, 1, 557-574. Gaunt, S. J. and Paul, Y.-L. (2011) Origins of Cdx1 regulatory elements suggest possible roles in vertebrate evolution. Int. J. Dev. Biol. 55, 93-98. Kreuger, F., Madeja, Z., Hemberger, M., McMahon, M., Cook, S. J. and Gaunt, S.J. (2009) Down-regulation of Cdx2 in colorectal carcinoma by the Raf-MEK-ERK 1/2 pathway. Cellular Signalling 21, 1846-1856. Benahmed, F., Jehan, E., Gaunt, S. J., Beck, F., Gross, I., Martin, E., Kedinger, M., Freund, J-N and Duluc, I. (2008) Multiple promoter regions control the complex expression pattern of the mouse Cdx2 homeobox gene. Gastroenterology, 135, 1238-1247. Gaunt, S. J., Drage, D. and Trubshaw, R. C. (2008) Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice. Development, 135, 2511-2520.