title: Formin1 mediates the induction of dendritogenesis and synaptogenesis by neurogenin3 in mouse hippocampal neurons.
abstract: Neurogenin3, a proneural transcription factor controlled by Notch receptor, has been recently shown to regulate dendritogenesis and synaptogenesis in mouse hippocampal neurons. However, little is known about the molecular mechanisms involved in these actions of Ngn3. We have used a microarray analysis to identify Ngn3 regulated genes related with cytoskeleton dynamics. One of such genes is Fmn1, whose protein, Formin1, is associated with actin and microtubule cytoskeleton. Overexpression of the Fmn1 isoform-Ib in cultured mouse hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs at 4 days in vitro. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritogenesis and synaptogenesis and indicate that this protein is a key component of the Ngn3 signaling pathway that controls neuronal differentiation.
authors.affiliation: Laboratory of Neuroactive Steroids, Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Simon-Areces
authors.forename: Ana
authors.initials: A
authors.lastname: Dopazo
authors.forename: Markus
authors.initials: M
authors.lastname: Dettenhofer
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rodriguez-Tebar
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Maria-Angeles
authors.initials: MA
authors.lastname: Arevalo
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D048430:Cell Shape; D002478:Cells, Cultured; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005971:Glutamates / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017729:Presynaptic Terminals / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005326:Fetal Proteins; D000080865:Formins; D005971:Glutamates; D049452:Green Fluorescent Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C407737:Neurog3 protein, mouse