title: ADAM10 negatively regulates neuronal differentiation during spinal cord development.
abstract: Members of the ADAM (a disintegrin and metalloprotease) family are involved in embryogenesis and tissue formation via their proteolytic function, cell-cell and cell-matrix interactions. ADAM10 is expressed temporally and spatially in the developing chicken spinal cord, but its function remains elusive. In the present study, we address this question by electroporating ADAM10 specific morpholino antisense oligonucleotides (ADAM10-mo) or dominant-negative ADAM10 (dn-ADAM10) plasmid into the developing chicken spinal cord as well as by in vitro cell culture investigation. Our results show that downregulation of ADAM10 drives precocious differentiation of neural progenitor cells and radial glial cells, resulting in an increase of neurons in the developing spinal cord, even in the prospective ventricular zone. Remarkably, overexpression of the dn-ADAM10 plasmid mutated in the metalloprotease domain (dn-ADAM10-me) mimics the phenotype as found by the ADAM10-mo transfection. Furthermore, in vitro experiments on cultured cells demonstrate that downregulation of ADAM10 decreases the amount of the cleaved intracellular part of Notch1 receptor and its target, and increases the number of βIII-tubulin-positive cells during neural progenitor cell differentiation. Taken together, our data suggest that ADAM10 negatively regulates neuronal differentiation, possibly via its proteolytic effect on the Notch signaling during development of the spinal cord.
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, School of Medicine University of Rostock, Rostock, Germany.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Key Laboratory for Medical Tissue Regeneration of Henan Province, Xinxiang Medical University, Xinxiang, P.R. China ; Institute of Anatomy I, School of Medicine University of Jena, Jena, Germany.
authors.forename: Juntang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, School of Medicine University of Rostock, Rostock, Germany.
authors.forename: Venkata Ajay Narendra
authors.initials: VA
authors.lastname: Talabattula
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, School of Medicine University of Rostock, Rostock, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Mußmann
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, School of Medicine University of Rostock, Rostock, Germany.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute of Anatomy, School of Medicine University of Rostock, Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, School of Medicine University of Rostock, Rostock, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, School of Medicine University of Rostock, Rostock, Germany.
authors.forename: Jiankai
authors.initials: J
authors.lastname: Luo
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002642:Chick Embryo; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human