The puzzle of Hox genes

In vertebrates, gastrulation is the crucial step that imparts the cues to the rostral-caudal patterning of the embryo's body. It is during this process that neural induction and anterior-posterior (A-P) regionalization in the neuroectoderm occur. Nieuwkoop's hypothesis suggests that these events are achieved in two steps: first, neural activation, driven by the prechordal mesoderm, converts competent ectoderm to anterior-specified neuroectoderm (i.e. "prosencephalic"). The neuroectoderm activated by the prechordal mesoderm is then converted to much posterior fates (i.e. hindbrain, spinal cord) by vertical contacts with the chordal mesoderm. Recent findings rescue the relevance of planar signals emanating from the organizer region before the involution of mesoderm over vertical interactions originated in the underlying dorsal mesoderm, during the establishment of embryonic A-P pattern. Treatments of vertebrate embryos with all trans retinoic acid (RA) during early development produce dramatic changes in the rostral-caudal axis that are correlated with profound alterations in the spatial expression of Hox-C genes, suggesting a relevant role of retinoids in rostral-caudal regionalization. Besides, genetic manipulations (overexpression and loss-of-function) of Hox-C genes provide strong support to the hypothesis that this gene family is involved in the patterning of the vertebrate A-P axis. In this review, we attempt to provide some clues for understanding the role of retinoids and Hox-C genes in the process of rostral-caudal regionalization.