Dr Stephen Gaunt

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. More recently, I have shown that the mouse Hoxc8 ‘early’ CRE is also regulated by Gdf11, but only in cooperation with a Cdx protein. Furthermore, Hoxb4, b8 and a7 CREs are activated by Cdx1 protein alone. These studies have developed use of cell culture to largely replace use of mice in the analysis of Hox gene enhancers.

Key Publications

Gaunt, S.J. (2022) Seeking sense in the Hox gene cluster. J. Dev. Biol. 10(4):48.

Gaunt, S.J. (2019) Made in the Image of a Fly. Amazon books and e.books ISBN: 9781691222674.

Gaunt, S.J. (2018) Hox cluster genes and collinearities throughout the tree of animal life. Int. J. Dev. Biol. 62:673-683.

Gaunt, S.J. (2015) The significance of Hox gene collinearity. Int. J. Dev. Biol. 59:159-170.

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., Drage, D. and Trubshaw, R.C. (2008) Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice. Development 135:2511-2520.

Coré, N., Bel, S., Gaunt, S.J., Aurrand-Lions, M., Pearce, J., Fisher, A. and Djabali, M. (1997) Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice. Development 124:721-729.

Gaunt, S.J. (1994) Conservation in the Hox code during morphological evolution. Int. J. Dev. Biol. 38:549-552.

Gaunt, S.J., Sharpe, P.T. and Duboule, D. (1988). Spatially restricted domains of homeo-gene transcripts in mouse embryos: relation to a segmented body plan. Development 104 Suppl. 169-179.

Gaunt, S.J., Miller, J.R., Powell, D.J. and Duboule D. (1986) Homeobox gene expression in mouse embryos varies with position by the primitive streak stage. Nature 324:662-664.