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Reciprocal gene replacements reveal unique functions for Phox2 genes during neural differentiation
journal contribution
posted on 2023-06-09, 06:56 authored by Eva Coppola, Alexandre Pattyn, Sarah GuthrieSarah Guthrie, Christo Goridis, Michèle StuderThe paralogous paired-like homeobox genes Phox2a and Phox2b are involved in the development of specific neural subtypes in the central and peripheral nervous systems. The different phenotypes of Phox2 knockout mutants, together with their asynchronous onset of expression, prompted us to generate two knock-in mutant mice, in which Phox2a is replaced by the Phox2b coding sequence, and vice versa. Our results indicate that Phox2a and Phox2b are not functionally equivalent, as only Phox2b can fulfill the role of Phox2a in the structures that depend on both genes. Furthermore, we demonstrate unique roles of Phox2 genes in the differentiation of specific motor neurons. Whereas the oculomotor and the trochlear neurons require Phox2a for their proper development, the migration of the facial branchiomotor neurons depends on Phox2b. Therefore, our analysis strongly indicates that biochemical differences between the proteins rather than temporal regulation of their expression account for the specific function of each paralogue.
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Publication status
- Published
Journal
EMBO JournalISSN
0261-4189Publisher
EMBO PressExternal DOI
Issue
24Volume
24Page range
4392-4403Department affiliated with
- Neuroscience Publications
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- No
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- Yes
Legacy Posted Date
2017-06-28Usage metrics
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