Article
- The EMBO Journal (2005) 24, 4392 - 4403
- doi:10.1038/sj.emboj.7600897
Published online: 1 December 2005
Subject Categories:
Reciprocal gene replacements reveal unique functions for Phox2 genes during neural differentiation
Eva Coppola1,2, Alexandre Pattyn3, Sarah C Guthrie2, Christo Goridis3 and Michèle Studer1
- TIGEM (Telethon Institute of Genetics and Medicine), Napoli, Italy
- MRC Centre for Developmental Neurobiology, King's College Guy's Campus; London, UK
- UMR 8542 CNRS, Département de Biologie, Ecole Normale Supérieure, Paris, France
Correspondence to:
Michèle Studer, TIGEM (Telethon Institute of Genetics and Medicin), Via P Castellino 111, Napoli 80131, Italy. Tel.: +39 081 6132 220; Fax: +39 081 560 9877; E-mail: studer@tigem.it
Received 10 August 2005; Accepted 10 November 2005
Abstract
The 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.
Keywords:
- facial branchiomotor neuron migration,
- knock-in,
- locus coerulus,
- oculomotor and trochlear neurons,
- Phox2 genes
