title: Discovery of a functional protein complex of netrin-4, laminin gamma1 chain, and integrin alpha6beta1 in mouse neural stem cells.
abstract: Molecular and cellular interactions coordinating the origin and fate of neural stem cells (NSCs) in the adult brain are far from being understood. We present a protein complex that controls proliferation and migration of adult NSCs destined for the mouse olfactory bulb (OB). Combinatorial selection based on phage display technology revealed a previously unrecognized complex between the soluble protein netrin-4 and laminin gamma1 subunit that in turn activates an alpha6beta1 integrin-mediated signaling pathway in NSCs. Differentiation of NSCs is accompanied by a decrease in netrin-4 receptors, indicating that netrin-4 participates in the continual propagation of this stem cell population. Notably, the stem cells themselves do not synthesize netrin-4. Further, we show that netrin-4 is produced by selected GFAP-positive astrocytes positioned close to newborn neurons migrating in the anterior part of the rostral migratory stream (RMS) and within the OB. Our findings present a unique molecular mechanism mediating astrocytic/neuronal crosstalk that regulates ongoing neurogenesis in the adult olfactory system.
authors.affiliation: David H. Koch Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Fernanda I
authors.initials: FI
authors.lastname: Staquicini
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dias-Neto
authors.forename: Jianxue
authors.initials: J
authors.lastname: Li
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Snyder
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sidman
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
mesh_terms: D000818:Animals; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D039121:Integrin alpha6beta1 / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology*; D000075385:Netrins; D009474:Neurons / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism; D011485:Protein Binding; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D039121:Integrin alpha6beta1; D007797:Laminin; D009414:Nerve Growth Factors; D000075385:Netrins; C416214:Ntn4 protein, mouse; C089141:laminin gamma 1