title: Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons.
abstract: The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening by in situ hybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner.
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Sato
authors.forename: Yuma
authors.initials: Y
authors.lastname: Fukutani
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tatara
authors.forename: Makoto
authors.initials: M
authors.lastname: Takemoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimamura
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003712:Dendrites / Q000187:drug effects*; D018274:Electroporation; D005260:Female; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D005822:Genetic Vectors; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D046228:Microarray Analysis; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000737:chemistry* / Q000502:physiology*; D014162:Transfection
chemical_list: D019138:Antibodies, Blocking; D017931:DNA Primers; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; C484539:NRN1 protein, human; D009479:Neuropeptides; C522413:VGF peptide