title: FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.
abstract: In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Murgan
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Aitana Manuela
authors.initials: AM
authors.lastname: Castro Colabianchi
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Renato José
authors.initials: RJ
authors.lastname: Monti
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Laura Elena
authors.initials: LE
authors.lastname: Boyadjián López
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Aguirre
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Ernesto González
authors.initials: EG
authors.lastname: Stivala
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Carrasco
authors.affiliation: Laboratorio de Embriología Molecular "Prof. Dr. Andrés E. Carrasco," Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Silvia L
authors.initials: SL
authors.lastname: López
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D036703:Blastula / Q000187:drug effects / Q000378:metabolism; D019521:Body Patterning / Q000187:drug effects; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism*; D047108:Embryonic Development / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000378:metabolism; D006257:Head / Q000002:abnormalities / Q000196:embryology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008648:Mesoderm / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D060172:Morpholinos / Q000494:pharmacology; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009672:Notochord / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D010641:Phenotype; D014981:Xenopus / Q000196:embryology* / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; C000598904:FoxA4 protein, Xenopus; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D060172:Morpholinos; D029867:Xenopus Proteins; C054234:chordin