title: Netrin1 is required for neural and glial precursor migrations into the olfactory bulb.
abstract: Netrin1 (NTN1) deficiency in mouse brain causes defects in axon guidance and cell migration during embryonic development. Here we show that NTN1 is required for olfactory bulb (OB) development at late embryogenesis and at early postnatal stages to facilitate the accumulation of proper numbers of granular and glomerular neuron subtypes and oligodendrocytes into the OB. In addition to the analysis of Ntn1-/- mice we made tissue and neurosphere cultures to clarify the role of NTN1 in the anterior forebrain. We propose that a subset of neural progenitors/precursors requires NTN1 to efficiently enter the rostral migratory stream to migrate into the OB. The analysis of postnatal Ntn1-/- OBs revealed a reduction of specific types of interneurons which have been shown to originate from particular subregions of the lateral ventricle walls. Based on Ntn1 expression in ventral parts of the ventricle walls, we observed a decrease in the mainly ventrally derived type II interneurons that express calcium-binding proteins calretinin and calbindin. Instead, no change in the numbers of dorsally derived tyrosine hydroxylase expressing interneurons was detected. In addition to the specific reduction of type II interneurons, our results indicate that NTN1 is required for oligodendroglial migration into the OB. Furthermore, we characterised the Ntn1 expressing subpopulation of neurosphere-forming cells from embryonic and adult brain as multipotent and self-renewing. However, NTN1 is dispensable for the proliferation of neurosphere forming progenitor cells and for their differentiation.
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöbergin katu 2, Helsinki, Finland. janne.hakanen@helsinki.fi
authors.forename: Janne
authors.initials: J
authors.lastname: Hakanen
authors.forename: Sébastien
authors.initials: S
authors.lastname: Duprat
authors.forename: Marjo
authors.initials: M
authors.lastname: Salminen
mesh_terms: D000818:Animals; D064032:Calbindin 2; D064026:Calbindins; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D007395:Interneurons; D020547:Lateral Ventricles / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C576511:Calb2 protein, mouse; D064032:Calbindin 2; D064026:Calbindins; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D064030:S100 Calcium Binding Protein G; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D014446:Tyrosine 3-Monooxygenase