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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Montavon, Thomas Le Garrec, Jean-François Kerszberg, Michel Duboule, Denis |
| Description | Country affiliation: Switzerland Author Affiliation: Montavon T ( National Research Centre Frontiers in Genetics, School of Life Sciences, Ecole Polytechnique Fédérale, CH-1015 Lausanne, Switzerland.) |
| Abstract | During the development of mammalian digits, clustered Hoxd genes are expressed following a collinear regulatory strategy, leading to both the growth of digits and their morphological identities. Because gene dosage is a key parameter in this system, we used a quantitative approach, associated with a collection of mutant stocks, to investigate the nature of the underlying regulatory mechanism(s). In parallel, we elaborated a mathematical model of quantitative collinearity, which was progressively challenged and validated by the experimental approach. This combined effort suggested a two-step mechanism, which involves initially the looping and recognition of the cluster by a complex including two enhancer sequences, followed by a second step of microscanning of genes located nearby. In this scenario, the respective rank of the genes, with respect to the 5' extremity of the cluster, is primordial, as well as different gene-specific affinities. This model accounts for the quantitative variations observed in our many mutant strains, and reveals the molecular constraint leading to thumbness; i.e., why a morphological difference must occur between the most anterior digit and the others. We also show that the same model applies to the collinear regulation of Hox genes during the emergence of external genitalia, though with some differences likely illustrating the distinct functionalities of these structures in adults. |
| File Format | HTM / HTML |
| ISSN | 08909369 |
| e-ISSN | 15495477 |
| DOI | 10.1101/gad.1631708 |
| Journal | Genes & Development |
| Issue Number | 3 |
| Volume Number | 22 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2008-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Extremities Embryology Gene Dosage Genes, Homeobox Physiology Models, Biological Animals Gene Expression Regulation, Developmental Mice Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Developmental Biology |
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