Contrôle des gènes Hox au cours du développement des vertébrés : apports de la transgenèse

Abstract

In Drosophila and vertebrates, the specification of structures along the anteroposterior (A/P) axis is controlled by the expression of a family of regulatory proteins. These products are encoded by a set of clustered genes called homeotics (in insects) or Hox genes (in vertebrates). The structural and functional organization of these gene families is conserved ; genes located at one physical extremity of the complexes specify anterior structures whereas genes at the other end control posterior structures. In Drosophila, the regulatory mechanisms involved in the expression of the homeotic genes are partially understood. In vertebrates, the anterior part is determined before the posterior following a progressive rostro-caudal morphogenetic progression. During the process, Hox genes are sequentially activated according to their position in the cluster in the order 3' early; 5' late (the temporal colinearity). Both structural and temporal colinearities, as well as the high degree of interspecies conservation of the HOX clusters, indicate an important function of such a structural organization. The analyses of transgenic embryos containing a Hox transcription unit with flanking sequences suggest, however, that a rather correct spatial regulation can be achieved when such a gene is removed from the complex. DNA regulatory sequences located at various places within several Hox loci can either display autonomous activities, e.g. by controlling the position of A/P boundaries and the tissue specificity, or selectively restrict the activity of a minimal Hox promoter. Altogether, these data suggest that multiple mechanisms of regulation act on the HOX complexes and that most of them are mediated by factors, possibly shared by neighbouring Hox genes, acting in trans. Such a regulation could explain the << clustered evolution >> of the Hox genes. Other possibilities are discussed.