title: A role for the hypoblast (AVE) in the initiation of neural induction, independent of its ability to position the primitive streak.
abstract: The mouse anterior visceral endoderm (AVE) has been implicated in embryonic polarity: it helps to position the primitive streak and some have suggested that it might act as a "head organizer", inducing forebrain directly. Here we explore the role of the hypoblast (the chick equivalent of the AVE) in the early steps of neural induction and patterning. We report that the hypoblast can induce a set of very early markers that are later expressed in the nervous system and in the forebrain, but only transiently. Different combinations of signals are responsible for different aspects of this early transient induction: FGF initiates expression of Sox3 and ERNI, retinoic acid can induce Cyp26A1 and only a combination of low levels of FGF8 together with Wnt- and BMP-antagonists can induce Otx2. BMP- and Wnt-antagonists and retinoic acid, in different combinations, can maintain the otherwise transient induction of these markers. However, neither the hypoblast nor any of these factors or combinations thereof can induce the definitive neural marker Sox2 or the formation of a mature neural plate or a forebrain, suggesting that the hypoblast is not a head organizer and that other signals remain to be identified. Interestingly, FGF and retinoids, generally considered as caudalizing factors, are shown here to play a role in the induction of a transient "pre-neural/pre-forebrain" state.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Albazerchi
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Stern
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics; D015415:Biomarkers; D040761:Biomimetic Materials / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004627:Embryonic Induction; D004707:Endoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology; D005775:Gastrula / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051857:Otx Transcription Factors / Q000235:genetics; D055748:SOXB1 Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C410845:ERNI protein, chicken; D006023:Glycoproteins; D006609:High Mobility Group Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D055748:SOXB1 Transcription Factors; C527786:Sox3 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D003577:Cytochrome P-450 Enzyme System; C054234:chordin