title: Epidermal induction and inhibition of neural fate by translation initiation factor 4AIII.
abstract: Bone Morphogenetic Protein-4 (BMP-4) is a potent epidermal inducer and inhibitor of neural fate. We have used differential screening to identify genes involved in epidermal induction downstream of BMP-4 and report here evidence of a novel translational mechanism that regulates the division of the vertebrate ectoderm into regions of neural and epidermal fate. In dissociated Xenopus ectoderm, addition of ectopic BMP-4 leads to an increase in the expression of translation initiation factor 4AIII (eIF-4AIII), a divergent member of the eIF-4A gene family until now characterized only in plants. In the gastrula embryo, Xenopus eIF-4AIII (XeIF-4AIII) expression is elevated in the ventral ectoderm, a site of active BMP signal transduction. Moreover, overexpression of XeIF-4AIII induces epidermis in dissociated cells that would otherwise adopt a neural fate, mimicking the effects of BMP-4. Epidermal induction by XeIF-4AIII requires both an active BMP signaling pathway and an extracellular intermediate. Our results suggest that XeIF-4AIII can regulate changes in cell fate through selective mRNA translation. We propose that BMPs and XeIF-4AIII interact through a positive feedback loop in the ventral ectoderm of the vertebrate gastrula.
authors.affiliation: Department of Vertebrate Embryology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Weinstein
authors.forename: E
authors.initials: E
authors.lastname: Honoré
authors.forename: A
authors.initials: A
authors.lastname: Hemmati-Brivanlou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D004475:Ectoderm / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction / Q000235:genetics; D004817:Epidermis / Q000196:embryology*; D039601:Eukaryotic Initiation Factor-4A; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D010448:Peptide Initiation Factors; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; D052004:Bone Morphogenetic Protein Receptors; D039601:Eukaryotic Initiation Factor-4A