title: Reciprocal gene replacements reveal unique functions for Phox2 genes during neural differentiation.
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.
authors.affiliation: TIGEM (Telethon Institute of Genetics and Medicine), Napoli, Italy, and MRC Centre for Developmental Neurobiology, King's College Guy's Campus, London, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Coppola
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pattyn
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Guthrie
authors.forename: Christo
authors.initials: C
authors.lastname: Goridis
authors.forename: Michèle
authors.initials: M
authors.lastname: Studer
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D018076:DNA, Complementary / Q000378:metabolism; D005724:Ganglia / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006720:Homozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D009802:Oculomotor Nerve / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014321:Trochlear Nerve / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D018398:Homeodomain Proteins; C109220:NBPhox protein; C491060:Phox2a protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors; D001616:beta-Galactosidase