Axon Growth and Survival (BIO 344) HS2024 PDF

Development of the Nervous System HS2024 BIO 344 Axon Growth and Survival Esther Stoeckli Dept. of Molecular Life Sciences University of Zurich ? The complexity of axon tracts increases rapidl...

Development of the Nervous System HS2024 BIO 344 Axon Growth and Survival Esther Stoeckli Dept. of Molecular Life Sciences University of Zurich ? The complexity of axon tracts increases rapidly during early stages of development Sanes, Reh, Harris, 2006 Axons have to: survive grow find and get to target recognize target connect to target  Neurons need trophic factors for survival DRG without with NGF DRG = dorsal root ganglion Viktor Hamburger (1900 - 2001) The discovery of Nerve Growth Factor (NGF) – the first neurotrophin Rita Levi-Montalcini 1909-2012 Nobel Prize 1986 in 2009 Reducing the target area enhances cell death during neural development limb bud control removed side The number of surviving neurons depends on the size of the target tissue grafting removal Sanes, Reh, Harris 2019 NGF (nerve growth factor) the first neurotrophic factor that was isolated Stanley Rita Cohen Levi-Montalcini Cells that die by apoptosis can be recognized by specific features Sanes, Reh, Harris 2019 Cell death by apoptosis requires protein synthesis Sanes, Harris, Reh 2012 Neurotrophins support survival of sensory neuron subtypes Chao, 2003 Neurotrophins are released in a target-specific manner Harrington & Ginty, 2013 Neurotrophins provide a means to adapt innervation to tissue size Sanes, Harris, Reh 2012 Neurotrophin signaling requires endocytosis and retrograde transport Harrington & Ginty, 2013 Neurotrophins prevent apoptosis and support synaptogenesis Harrington & Ginty, 2013 Axons have to: survive grow find and get to target recognize target connect to target Axons extend long processes to connect to their targets Axons extend long processes to connect to their targets  Axons grow by adding new microtubules at the distal end Sanes, Reh, Harris, 2006  Axons grow by stretching Sanes, Reh, Harris, 2006 The shape of the growth cone differs depending on the environment or the „growth phase“ of the axon Sanes, Reh, Harris, 2006 Sanes, Reh, Harris, 2006 Sanes, Reh, Harris, 2006  The speed of the growth cone depends on the location Sanes, Reh, Harris, 2006 Non-permissive substrates induce turns of growth cones at the substratum boundary In vertebrate growth cones actin filaments and microtubules meet in the peripheral zone actin filaments microtubules Dent et al., Cold Spring Harb Perspect Biol 2011 Actin and tubulin form elements of the growth cone‘s cytoskeleton Lowery & Van Vactor 2009  Figure 1 Treadmilling cycle of actin filaments at steady state. Profilin Cofilin Gungabissoon R A , Bamburg J R J Histochem Cytochem 2003;51:411-420 Copyright © by The Histochemical Society Actin filaments and microtubules are in a ‚dymamic steady-state‘ Lowery & Van Vactor 2009  Filopodia can exert force Sanes, Reh, Harris, 2006  Filopodia induce growth cone turning Sanes, Reh, Harris, 2006  The cytoskeleton steers the growth cone in vitro Depolymerization of actin filaments induces a turn of the growth cone in direction of the intact filaments Sanes, Reh, Harris, 2006 Stabilization of microtubules induces a turn of the growth cone in direction of the stabilized microtubules Sanes, Reh, Harris, 2006 Destabilization of microtubules induces a turn of the growth cone in direction of the stable microtubules Sanes, Reh, Harris, 2006 Information derived from the interaction of surface receptors with guidance cues is transmitted to the cytoskeleton Dickson, 2002  Four mechanisms cooperate to guide axons Tessier-Lavigne and Goodman, Science, 1996  Actin filaments are required for axon guidance Sanes, Reh, Harris, 2006  The clutch mechanism explains how traction is generated to move the growth cone forward Sanes, Reh, Harris, 2006 Signal transduction pathway linking Rho GTPases to the cytoskeleton  Axon branching is important for neuronal connectivity Gallo, Dev. Neurobiol. 71(2011)201-220 Axon collaterals form by a well-orchestrated sequence of cytoskeletal changes Gallo, Dev. Neurobiol. 71(2011)201-220 Branch formation requires actin filaments and microtubules Winkle et al., Dev. Neurobiol. 76(2016)1293 Which molecules act as guidance cues (or their receptors)? How many are there? Do all axons listen to the same guidance cues?