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