title: ADF/cofilin-mediated actin retrograde flow directs neurite formation in the developing brain.
abstract: Neurites are the characteristic structural element of neurons that will initiate brain connectivity and elaborate information. Early in development, neurons are spherical cells but this symmetry is broken through the initial formation of neurites. This fundamental step is thought to rely on actin and microtubule dynamics. However, it is unclear which aspects of the complex actin behavior control neuritogenesis and which molecular mechanisms are involved. Here, we demonstrate that augmented actin retrograde flow and protrusion dynamics facilitate neurite formation. Our data indicate that a single family of actin regulatory proteins, ADF/Cofilin, provides the required control of actin retrograde flow and dynamics to form neurites. In particular, the F-actin severing activity of ADF/Cofilin organizes space for the protrusion and bundling of microtubules, the backbone of neurites. Our data reveal how ADF/Cofilin organizes the cytoskeleton to drive actin retrograde flow and thus break the spherical shape of neurons.
authors.affiliation: Max Planck Institute of Neurobiology, Axonal Growth and Regeneration Group, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Flynn
authors.forename: Farida
authors.initials: F
authors.lastname: Hellal
authors.forename: Dorothee
authors.initials: D
authors.lastname: Neukirchen
authors.forename: Sonja
authors.initials: S
authors.lastname: Jacob
authors.forename: Sabina
authors.initials: S
authors.lastname: Tahirovic
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dupraz
authors.forename: Sina
authors.initials: S
authors.lastname: Stern
authors.forename: Boyan K
authors.initials: BK
authors.lastname: Garvalov
authors.forename: Christine
authors.initials: C
authors.lastname: Gurniak
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Shaw
authors.forename: Liane
authors.initials: L
authors.lastname: Meyn
authors.forename: Roland
authors.initials: R
authors.lastname: Wedlich-Söldner
authors.forename: James R
authors.initials: JR
authors.lastname: Bamburg
authors.forename: J Victor
authors.initials: JV
authors.lastname: Small
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
authors.forename: Frank
authors.initials: F
authors.lastname: Bradke
mesh_terms: D051339:Actin Depolymerizing Factors / Q000502:physiology*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D048708:Cell Growth Processes / Q000502:physiology; D048430:Cell Shape / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D051345:Destrin / Q000502:physiology*; D020439:Growth Cones / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000502:physiology; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D051345:Destrin; C495825:Dstn protein, mouse