title: Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons.
abstract: Final morphological polarization of neurons, with the development of a distinct axon and several dendrites, is preceded by phases where they have a non-polarized architecture. The earliest of these phases is that of the round neuron arising from the last mitosis. A second non-polarized stage corresponds to the bipolar neuron, with two morphologically identical neurites. Both phases have their distinctive relevance in the establishment of neuronal polarity. During the round cell stage, a decision is made as to where from the cell periphery a first neurite will form, thus creating the first sign of asymmetry. At the bipolar stage a decision is made as to which of the two neurites becomes the axon in neurons polarizing in vitro, and the leading edge in neurons in situ. In this study, we analysed cytoskeletal and membrane dynamics in cells at these two 'pre-polarity' stages. By means of time lapse imaging in dissociated hippocampal neurons and ex vivo cortical slices, we show that both stages are characterized by polarized intracellular arrangements. However, the stages have distinct temporal hierarchies: polarized actin dynamics marks the site of first polarization in round cells, whereas polarized membrane dynamics precedes asymmetric growth in the bipolar stage.
authors.affiliation: VIB Center for the Biology of Disease, KULeuven Center for Human Genetics, Leuven, Belgium and KULeuven, Department of Development and Regeneration, 3000 Leuven, Belgium Annette.Gaertner@cme.vib-kuleuven.be cdotti@cbm.csic.es.
authors.forename: Annette
authors.initials: A
authors.lastname: Gärtner
authors.affiliation: S. Raffaele Scientific Institute/Vita-Salute University, Neuropsychopharmacology Unit, Division of Neuroscience, 20132 Milan, Italy.
authors.forename: Eugenio F
authors.initials: EF
authors.lastname: Fornasiero
authors.affiliation: S. Raffaele Scientific Institute/Vita-Salute University, Neuropsychopharmacology Unit, Division of Neuroscience, 20132 Milan, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Valtorta
authors.affiliation: VIB Center for the Biology of Disease, KULeuven Center for Human Genetics, Leuven, Belgium and KULeuven, Department of Development and Regeneration, 3000 Leuven, Belgium Centro de Biología Molecular Severo Ochoa, CSIC/UAM, 28049 Madrid, Spain Annette.Gaertner@cme.vib-kuleuven.be cdotti@cbm.csic.es.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Dotti
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development*; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D021381:Protein Transport; D051381:Rats; D011919:Rats, Inbred Strains; D059008:Time-Lapse Imaging
chemical_list: D000199:Actins
keywords: Axon; FRAP; Membrane traffic; Migration; Neuron; Polarity