Coordination of Hox identity between germ layers along the anterior-to-posterior axis of the vertebrate embryo

During early embryonic development, a relatively undifferentiated mass of cells is shaped into a complex and morphologically differentiated embryo. This is achieved by a series of coordinated cell movements that end up in the formation of the three germ layers of most metazoans and the establishment of the body plan. Hox genes are among the main determinants in this process and they have a prominent role in granting identity to different regions of the embryo. The particular arrangement of their expression domains in early development corresponds to and characterises several future structures of the older embryo and adult animal. Getting to know the molecular and cellular phenomena underlying the correct Hox pattern will help us understand how the complexity of a fully-formed organism can arise from its raw materials, a relatively undifferentiated fertilised egg cell (zygote) and a large but apparently limited repertoire of molecular agents. In the present work I have concentrated on the specific factors, and their mechanism of action, that set up the Hox expression patterns in the gastrula and neurula embryo. I have put special emphasis on the initiation of Hox expression, which takes place first in the non-organiser mesoderm and subsequently in the neuroectoderm. I investigated the role of retinoid signalling and found that it is required during late gastrulation for activation of 3’ Hox genes in the neuroectoderm. Furthermore, I show evidence that the earliest phase of expression in the gastrula mesoderm requires Wnt, but not retinoid, activity. Moreover, the most 3’ Hox genes are direct targets of the Wnt pathway, whereas other Hox genes are indirectly regulated. Finally, I provide preliminary results that suggest a potential mechanism for communication between non-organiser mesoderm and neuroectoderm mediated by HOX protein intercellular signalling. This phenomenon would enable a direct coordination of Hox pattern between the two tissues