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A balance between the anti-apoptotic activity of Slug and the apoptotic activity of msx1 is required for the proper development of the neural crest
We have studied the pattern of programmed cell death in the neural crest and analyzed how it is controlled by the activity of the transcription factors Slug and msx1. Our results indicate that apoptosis is more prevalent in the neural folds than in the rest of the neural ectoderm. Through gain- and...
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Published in: | Developmental biology 2004-11, Vol.275 (2), p.325-342 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | We have studied the pattern of programmed cell death in the neural crest and analyzed how it is controlled by the activity of the transcription factors
Slug and
msx1. Our results indicate that apoptosis is more prevalent in the neural folds than in the rest of the neural ectoderm. Through gain- and loss-of-function experiments with inducible forms of both
Slug and
msx1 genes, we showed that
Slug acts as an anti-apoptotic factor whereas
msx1 promotes cell death, either in the neural folds of the whole embryos, in isolated or induced neural crest and in animal cap assays. The protective effect of expressing
Slug can be reversed by expressing the apoptotic factor
Bax, while the apoptosis promoted by
msx1 can be abolished by expressing the
Xenopus homologue of
Bcl2 (
XR11). Furthermore, we show that
Slug and
msx1 control the transcription of
XR11 and several caspases required for programmed cell death. In addition, expression of
Bax or
Bcl2, produced similar effects on the survival of the neural crest and on the development of its derivatives to those produced by altering the activity of
Slug or
msx1. Finally, we show that in the neural crest, the region of the neural folds where
Slug is expressed, cells undergo less apoptosis, than in the region where the
msx1 gene is expressed, which correspond to cells adjacent to the neural crest. We show that the expression of
Slug and
msx1 controls cell death in certain areas of the neural folds, and we discuss how this equilibrium is necessary to generate sharp boundaries in the neural crest territory, and to precisely control cell number among neural crest derivatives. |
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ISSN: | 0012-1606 1095-564X |
DOI: | 10.1016/j.ydbio.2004.07.041 |