title: Xrx1 controls proliferation and neurogenesis in Xenopus anterior neural plate.
abstract: In Xenopus neuroectoderm, posterior cells start differentiating at the end of gastrulation, while anterior cells display an extended proliferative period and undergo neurogenesis only at tailbud stage. Recent studies have identified several important components of the molecular pathways controlling posterior neurogenesis, but little is known about those controlling the timing and positioning of anterior neurogenesis. We investigate the role of Xrx1, a homeobox gene required for eye and anterior brain development, in the control of proliferation and neurogenesis of the anterior neural plate. Xrx1 is expressed in the entire proliferative region of the anterior neural plate delimited by cells expressing the neuronal determination gene X-ngnr-1, the neurogenic gene X-Delta-1, and the cell cycle inhibitor p27Xic1. Positive and negative signals position Xrx1 expression to this region. Xrx1 is activated by chordin and Hedgehog gene signaling, which induce anterior and proliferative fate, and is repressed by the differentiation-promoting activity of neurogenin and retinoic acid. Xrx1 is required for anterior neural plate proliferation and, when overexpressed, induces proliferation, inhibits X-ngnr-1, X-Delta-1 and N-tubulin and counteracts X-ngnr-1- and retinoic acid-mediated differentiation. We find that Xrx1 does not act by increasing lateral inhibition but by inducing the antineurogenic transcriptional repressors Xhairy2 and Zic2, and by repressing p27Xic1. The effects of Xrx1 on proliferation, neurogenesis and gene expression are restricted to the most rostral region of the embryo, implicating this gene as an anterior regulator of neurogenesis.
authors.affiliation: Dipartimento di Fisiologia e Biochimica, Università degli Studi di Pisa, Via Carducci 13, 56010 Ghezzano (Pisa), Italy. andream@dfb.unipi.it
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Andreazzoli
authors.forename: Gaia
authors.initials: G
authors.lastname: Gestri
authors.forename: Federico
authors.initials: F
authors.lastname: Cremisi
authors.forename: Simona
authors.initials: S
authors.lastname: Casarosa
authors.forename: Igor B
authors.initials: IB
authors.lastname: Dawid
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barsacchi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D009024:Morphogenesis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000033:anatomy & histology / Q000196:embryology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014212:Tretinoin; D029867:Xenopus Proteins; C524416:Rax protein, Xenopus; C112757:Zic2 protein, Xenopus; C101907:neurogenin, Xenopus