title: A disintegrin and metalloprotease 21 (ADAM21) is associated with neurogenesis and axonal growth in developing and adult rodent CNS.
abstract: We have reported that alpha6beta1 integrin regulates the directed migration of neuroblasts from the adult rodent subventricular zone (SVZ) through the rostral migratory stream (RMS). ADAM (a disintegrin and metalloprotease) proteins bind integrins. Here, we show that ADAM21, but not ADAM2, -3, -9, -10, -12, -15, or -17, is expressed in adult rats and mice by ependyma and SVZ cells with long basal processes, and in radial glia at early postnatal times. ADAM21-positive processes projected into the RMS, contacted blood vessels, and were present within the RMS intermingled with neuroblasts up to where neuroblasts start their radial migration and differentiation in the olfactory bulb. Tissue inhibitors of metalloproteases (TIMPs) 1, 2, and 3 are present in the ependymal layer but not in the SVZ and RMS. Thus, ADAM21 could regulate neurogenesis and guide neuroblast migration through cleavage-dependent activation of proteins and integrin binding. ADAM21 is also present in growing axonal tracts during postnatal development and in growing primary olfactory axons in adults. In the olfactory nerve layer, ADAM21 often, but not always, colocalizes with OMP, a marker of mature olfactory neurons, but is not colocalized with the immature marker betaIII-tubulin. This suggests that ADAM21 is involved in the final axonal outgrowth phase and/or synapse formation. TIMP3 is present in periglomerular neurons, where it could restrict ADAM21-mediated axonal growth to the glomeruli. ADAM21's unique disintegrin and metalloprotease sequences and its restricted expression suggest that it might be a good target for influencing neurogenesis and neuronal plasticity.
authors.affiliation: Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, 511 S. Floyd Street, Louisville, KY 40292, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: K Adam
authors.initials: KA
authors.lastname: Baker
authors.forename: Theo
authors.initials: T
authors.lastname: Hagg
mesh_terms: D051722:ADAM Proteins; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D039121:Integrin alpha6beta1 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D051842:Olfactory Marker Protein; D038081:Organogenesis; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011938:Rec A Recombinases / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D039121:Integrin alpha6beta1; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D014404:Tubulin; D014746:Vimentin; D011938:Rec A Recombinases; D051722:ADAM Proteins; C409065:Adam21 protein, mouse; D008666:Metalloendopeptidases; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine