Conséquences embryologiques d'une dérégulation contrôlée de l'homéogène murin Hoxa2
(2004)
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- Abstract
- Hox homeotic genes encode homeodomain transcription factors implicated in embryonic patterning. Among them, Hoxa2 is transiently expressed in the second branchial arch and confers their identity to its skeletal derivatives. Although the functional significance of the gene's expression pattern is progressively better understood, nothing is known yet about the meaning of its temporal expression dynamic. Aiming to address this question, we generated a transgenic mouse line for a conditional Hoxa2 misregulation. Based on the prokaryotic Cre/loxP recombination system, this line allows to specifically direct the homeogene's expression in any tissue and at any time during mouse development. Hoxa2 expression is normally turned off in differentiating branchial skeleton and, to better understand the meaning of this precise temporal dynamic, we used our transgenic line to force the homeogene's expression in all differentiating cartilages. Here, we show that transgenics for a Collagen type II directed Hoxa2 expression suffer of letal chondrodysplasia probably due to impaired prechondroblasts differentiation. Consistently, although no major patterning or proliferation defects were observed, each cartilaginous differentiation step was severely affected in mutant mice. In the last third of gestation, while a strong cartilaginous skeleton is clearly visible in wild type embryos, mutants only harbour coastal and cervical rudiments. Later on, cartilages hypertrophy, mineralization and ossification are all delayed in such individuals. Ongoing experiments intend to identify the precise molecular causes to the reported chondrodysplasia. For the first time here, we clearly uncoupled a Hox factor's patterning function from its antidifferentiating potential. This study shows that an important function of Hoxa2 during skeletogenesis, is to keep precursor cells undifferentiated until they reach their final embryonic location. There, Hoxa2 must be necessary turned off for differentiation to proceed.
- Affiliations
UCLouvain SC/BIOL - Département de biologie
Citations
Massip, L. (2004). Conséquences embryologiques d’une dérégulation contrôlée de l’homéogène murin Hoxa2. https://hdl.handle.net/2078.5/97492