Juan-Carlos Izpisúa-Belmonte

The Hox-4.8 gene is localized at the 5" extremity of the Hox-4 complex and is expressed in the most posterior parts of the body during development

We report the isolation and expression pattern of a novel mouse homeobox gene, Hox-4.8. Hox-4.8 is the most 5-located homeobox gene in the HOX-4 complex. Sequence analysis confirmed that Hox-4.8 is a member of the subfamily of AbdominalB-related Hox-4 genes and revealed strong interspecies conservation. As for the human locus, Hox-4.8 is probably the last Hox gene in this part of the HOX-4 complex. During development, Hox-4.8 transcripts are restricted to the extremities of the embryonic anteroposterior axis and limbs as well as in the developing tail bud and to the most posterior segment of the gut (the rectum). Within the limb mesenchyme, Hox-4.8 is expressed in more posterodistal regions than those of its neighbour Hox-4.7. Hence, Hox-4.8 expression appears to be related to the last significant phenotypic changes towards the extremities of the embryonic body and limb axes.

Homeobox genes and pattern formation in the vertebrate limb

The developing vertebrate limb is a powerful system to study genes potentially involved in pattern formation. Many such candidate genes encode transcription factors belonging to the class of the homeodomain proteins. In this short review, we discuss the possible functions of different subfamilies of homeobox genes. Genes belonging to the Hox family (related to the Drosophila homoeotic genes), such as the HOX-1, HOX-3, and HOX-4, complexes are probably among those encoding the patterning information. Their differential expression in the mesenchymal compartment is proposed to be responsible for the determination of the various axial elements. Other homeobox-containing genes are expressed in both the mesenchyme of the progress zone and the ectodermal ridge. These genes, Hox-7.1 and Hox-8.1, are related to the Drosophila msh gene and could be involved in epithelial-mesenchymal interactions linking the growth of the system to its patterning.

Sonic Hedgehog (shh) expression in developing and regenerating axolotl limbs

Sonic hedgehog (shh) expression is detectable in the posterior mesenchyme of many developing vertebrate limbs. We have isolated an RT-PCR fragment from the axolotl, Ambystoma mexicanum, that has high identity to other vertebrate shh genes. We describe the localization of this transcript during development and regeneration and in response to tissue grafts and retinoic acid (RA) exposure in the axolotl. Even though axolotl digits show a reversed polarity of differentiation (anterior [A] to posterior [P]) when compared to other tetrapods (P to A), shh is nevertheless expressed on the posterior margin of developing and regenerating limb buds. When A cells are grafted adjacent to P cells, an ectopic domain of shh is induced. Exposure to retinoic acid (RA), a molecule known to alter pattern in all three limb axes in urodeles, results in ectopic expression of shh in anterior cells of the regeneration blastema. Prior to this induced expression in response to RA, there is an earlier response by the endogenous domain of shh, which is downregulated within the first few hours of exposure.

Teleost HoxD and HoxA genes: comparison with tetrapods and functional evolution of the HOXD complex

In tetrapods, Hox genes are essential for the proper organization and development of axial structures. Experiments involving Hox gene inactivations have revealed their particularly important functions in the establishment of morphological transitions within metameric series such as the vertebral column. Teleost fish show a much simpler range of axial (trunk or appendicular) morphologies, which prompted us to investigate the nature of the Hox system in these lower vertebrates. Here, we show that fish have a family of Hox genes, very similar in both number and general organization, to that of tetrapods. Expression studies, carried out with HoxD and HoxA genes, showed that all vertebrates use the same general scheme, involving the colinear activation of gene expression in both space and time. Comparisons between tetrapods and fish allowed us to propose a model which accounts for the primary function of this gene family. In this model, a few ancestral Hox genes were involved in the determination of polarity in the digestive tract and were further recruited in more elaborate axial structures.

Origin and development of the avian tongue muscles.

u2002The musculature of the vertebrate tongue is composed of cells recruited from the somites. In this paper we have investigated the migration and organisation of the muscle cells that give rise to the tongue muscle during chick embryogenesis. At the molecular level, our data suggests that a population of Tbx-3 expressing cells migrate away from the occipital somites prior to the migration of muscle precursors that express Pax-3. Both populations take the same pathway and form the hypoglossal cord. The first signs of muscle cell differentiation were not detected until cells had migrated some distance from the somites. We have determined the contribution of single somites to the musculature of the tongue and show in contrast to previous data that somites 2–6 take part in the formation of all glossal and infrahyoid muscles to the same extent but do not contribute to suprahyoid muscle. This is particularly interesting since glossal and infrahyoid muscle differ from the suprahyoid muscles not only in their morphology, but also in their developmental origin. Furthermore we show that myocytes cross the midline and contribute to the contralateral glossal and infrahyoid muscles. This is supported from our molecular data, which showed that the migratory precursor population was maintained primarily at the rostral tip of the developing hypoglossal cord.

The murine even-skipped-like gene Evx-2 is closely linked to the Hox-4 complex, but is transcribed in the opposite direction

Note: Max-Planck-Institute of Biophysical Chemistry, Department of Molecular Cell Biology, Gottingen, FRG. Reference UPDUB-ARTICLE-1992-001doi:10.1007/BF00355726 Record created on 2008-02-25, modified on 2017-05-12