Transformations in null mutants of Hox genes: do they represent intercalary
regenerates?

Crawford MJ

Institut de Recherches Cliniques de Montreal, Quebec, Canada.

In the minds of many, Hox gene null mutant phenotypes have confirmed the direct
role that these genes play in specifying the pattern of vertebrate embryos. The
genes are envisaged as defining discrete spatial domains and, subsequently,
conferring specific segmental identities on cells undergoing differentiation
along the antero-posterior axis. However, several aspects of the observed mutant
phenotypes are inconsistent with this view. These include: the appearance of
other, unexpected transformations along the dorsal axis; the occurrence of
mirror-image duplications; and the development of anomalies outside the
established domains of normal Hox gene expression. In this paper, Hox gene
disruptions are shown to elicit regeneration-like responses in tissues
confronted with discontinuities in axial identity. The polarities and
orientations of transformed segments which emerge as a consequence of this
response obey the rules of distal transformation and intercalary regeneration.
In addition, the incidence of periodic anomalies suggests that the initial steps
of Hox-mediated patterning occurs in Hensen's node. As gastrulation proceeds,
mesoderm cell cycle kinetics impose constraints upon subsequent cellular
differentiation. This results in the delayed manifestation of transformations
along the antero-posterior axis. Finally, a paradigm is sketched in which
temporal, rather than spatial axial determinants direct differentiation.
Specific, testable predictions are made about the role of Hox genes in the
establishment of segmental identity.
 

PMID: 8634068, UI: 96112768