title: The pro-apoptotic activity of a vertebrate Bar-like homeobox gene plays a key role in patterning the Xenopus neural plate by limiting the number of chordin- and shh-expressing cells.
abstract: Targeted disruption of effectors molecules of the apoptotic pathway have demonstrated the occurrence and magnitude of early programmed cell death (EPCD), a form of apoptosis that affects proliferating and newly differentiated cells in vertebrates, and most dramatically cells of the central nervous system (CNS). Little is known about the molecular pathways controlling apoptosis at these early developmental stages, as the roles of EPCD during patterning of the developing nervous system. We describe a new function, in Xenopus neurodevelopment, for a highly conserved homeodomain protein Barhl2. Barhl2 promotes apoptosis in the Xenopus neuroectoderm and mesoderm, acting as a transcriptional repressor, through a mechanism that cannot be attributed to an unspecific cellular stress response. We show that the pro-apoptotic activity of Barhl2 is essential during normal neural plate formation as it limits the number of chordin- and Xshh-expressing cells in the prospective notochord and floorplate, which act as organizing centers. Our findings show that Barhl2 is part of a pathway regulating EPCD. They also provide evidence that apoptosis plays an important role in regulating the size of organizing centers.
authors.affiliation: Unité Rétrovirus et Transfert Génétique, INSERM (U622). Institut Pasteur, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Offner
authors.forename: Nathalie
authors.initials: N
authors.lastname: Duval
authors.forename: Milan
authors.initials: M
authors.lastname: Jamrich
authors.forename: Béatrice
authors.initials: B
authors.lastname: Durand
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D019521:Body Patterning / Q000235:genetics*; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism; D016000:Cluster Analysis; D017931:DNA Primers; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005697:Galactosides; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C501324:Barhl2 protein, Xenopus; D017931:DNA Primers; D005697:Galactosides; D006023:Glycoproteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; C054234:chordin; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside