| | |  | | | | Record from Web of Science® | | | | | | |
| THE ROLE OF HOXA-3 IN MOUSE THYMUS AND THYROID DEVELOPMENT |
|
|
| Author(s): MANLEY NR, CAPECCHI MR |
| Source: DEVELOPMENT Volume: 121 Issue: 7 Pages: 1989-2003 Published: JUL 1995 |
| Times Cited: 230 References: 58 |
| Abstract: Targeted disruption of Hoxa-3 results in a number of regionally restricted defects in tissues and structures derived from or patterned by mesenchymal neural crest. However, analysis of mutant embryos with injections of a carbocyanine dye or with molecular markers that label these cells indicates that neither the amount nor the migration patterns of this neural crest population are grossly affected. Therefore, it appears that the loss of Hoxa-3 affects the intrinsic capacity of this neural crest cell population to differentiate and/or to induce proper differentiation of the surrounding pharyngeal arch and pouch tissues. Hoxa-3 mutant mice are athymic and show thyroid hypoplasia. Thymus development is first evident as an expansion of mesenchymal neural crest in the posterior part of the 3rd pharyngeal pouch. Prior to this expansion, a marked reduction in pax-1 expression is observed in these cells in the mutant embryos. As pax-1 mutant mice also show thymic hypoplasia, these results suggest that Hoxa-3 may be required to maintain pax-1 expression in these cells and that the reduction of pax-1 expression is part of the athymic teleology in Hoxa-3 mutant mice. The thyroid gland is formed from the fusion of two structures of separate embryonic origin, the thyroid diverticulum, which is formed from endodermal epithelium in the floor of the pharynx, and the ultimobranchial body, formed from mesenchymal neural crest in the 4th pharyngeal pouch. Both of these sites express Hoxa-3 and are defective in mutant mice, Often a vesicle is observed in mutant mice that is exclusively composed of calcitonin-producing cells, suggesting the persistence of an ultimobranchial body. Both aspects of the thyroid phenotype show variable expressivity among mutant animals, even on the two sides of the same mutant animal. This variability suggests the presence of a compensating gene or genes, whose utilization is stochastic. A reasonable candidate for providing this compensatory function is the paralogous gene Hoxb-3. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV UTAH, SCH MED, HOWARD HUGHES MED INST, DEPT HUMAN GENET, SALT LAKE CITY, UT 84112 USA |
| Publisher: COMPANY OF BIOLOGISTS LTD, BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL |
| Subject Category: Developmental Biology |
| IDS Number: RH141 |
| ISSN: 0950-1991 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |