Long-Range Optogenetic Control of Axon Guidance Overcomes Developmental Boundaries and Defects.

axon guidance axons embryonic development nerve regeneration neuronal outgrowth neurons optogenetics rac GTP-binding proteins tissue engineering zebrafish

Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
08 06 2020
Historique:
received: 25 04 2019
revised: 12 03 2020
accepted: 11 05 2020
entrez: 10 6 2020
pubmed: 10 6 2020
medline: 2 1 2021
Statut: ppublish

Résumé

Axons connect neurons together, establishing the wiring architecture of neuronal networks. Axonal connectivity is largely built during embryonic development through highly constrained processes of axon guidance, which have been extensively studied. However, the inability to control axon guidance, and thus neuronal network architecture, has limited investigation of how axonal connections influence subsequent development and function of neuronal networks. Here, we use zebrafish motor neurons expressing a photoactivatable Rac1 to co-opt endogenous growth cone guidance machinery to precisely and non-invasively direct axon growth using light. Axons can be guided over large distances, within complex environments of living organisms, overriding competing endogenous signals and redirecting axons across potent repulsive barriers to construct novel circuitry. Notably, genetic axon guidance defects can be rescued, restoring functional connectivity. These data demonstrate that intrinsic growth cone guidance machinery can be co-opted to non-invasively build new connectivity, allowing investigation of neural network dynamics in intact living organisms.

Identifiants

pubmed: 32516597
pii: S1534-5807(20)30398-1
doi: 10.1016/j.devcel.2020.05.009
pmc: PMC7375170
mid: NIHMS1601612
pii:
doi:

Substances chimiques

Zebrafish Proteins 0
rac1a protein, zebrafish 0
rac1 GTP-Binding Protein EC 3.6.5.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

577-588.e7

Subventions

Organisme : NIMH NIH HHS
ID : P50 MH094271
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA103846
Pays : United States
Organisme : NINDS NIH HHS
ID : U19 NS104653
Pays : United States
Organisme : NINDS NIH HHS
ID : F30 NS095520
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH115727
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests L.I.Z. is a founder and stockholder of Fate Therapeutics, Scholar Rock, Amagma Therapeutics, and CAMP4 Therapeutics. He is a consultant for Celularity and Cellarity. P.A. is a consultant for System1 Biosciences, Foresite Labs and Flagship Labs 60. A patent application is pending based on this work (applicants: President and Fellows of Harvard College; inventors: P.A. and J.M.H.; status: pending; aspect covered: methods and apparatus for optogenetic control of neurite growth). All other authors declare no competing interests.

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Auteurs

James M Harris (JM)

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA.

Andy Yu-Der Wang (AY)

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

Jonathan Boulanger-Weill (J)

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

Cristina Santoriello (C)

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stem Cell Program and Division of Hematology/Oncology, Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02115, USA.

Stephan Foianini (S)

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

Jeff W Lichtman (JW)

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.

Leonard I Zon (LI)

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stem Cell Program and Division of Hematology/Oncology, Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02115, USA.

Paola Arlotta (P)

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA. Electronic address: paola_arlotta@harvard.edu.

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