Environmental Elasticity Regulates Cell-type Specific RHOA Signaling and Neuritogenesis of Human Neurons

Bibliographic Details
Title: Environmental Elasticity Regulates Cell-type Specific RHOA Signaling and Neuritogenesis of Human Neurons
Authors: Robert H. Nichol, IV, Timothy S. Catlett, Massimo M. Onesto, Drew Hollender, Timothy M. Gómez
Source: Stem Cell Reports, Vol 13, Iss 6, Pp 1006-1021 (2019)
Publisher Information: Elsevier, 2019.
Publication Year: 2019
Collection: LCC:Medicine (General)
LCC:Biology (General)
Subject Terms: Medicine (General), R5-920, Biology (General), QH301-705.5
More Details: Summary: The microenvironment of developing neurons is a dynamic landscape of both chemical and mechanical cues that regulate cell proliferation, differentiation, migration, and axon extension. While the regulatory roles of chemical ligands in neuronal morphogenesis have been described, little is known about how mechanical forces influence neurite development. Here, we tested how substratum elasticity regulates neurite development of human forebrain (hFB) neurons and human motor neurons (hMNs), two populations of neurons that naturally extend axons into distinct elastic environments. Using polyacrylamide and collagen hydrogels of varying compliance, we find that hMNs preferred rigid conditions that approximate the elasticity of muscle, whereas hFB neurons preferred softer conditions that approximate brain tissue elasticity. More stable leading-edge protrusions, increased peripheral adhesions, and elevated RHOA signaling of hMN growth cones contributed to faster neurite outgrowth on rigid substrata. Our data suggest that RHOA balances contractile and adhesive forces in response to substratum elasticity. : Axons extend through varying tissue elasticities in vivo, but it is unknown how tissue mechanics influence neuron development. In this article, Gómez and colleagues examine how substratum elasticity affects process formation by human motor and forebrain neurons. They show that motor neurons extend axons best on more rigid conditions compared with forebrain neurons, which is due to differences in RHOA-mediated adhesion. Keywords: mechanotransduction, RHOA, adhesion signaling, axon outgrowth, growth cone, iPSC, regeneration, cortical neuron
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2213-6711
Relation: http://www.sciencedirect.com/science/article/pii/S2213671119303698; https://doaj.org/toc/2213-6711
DOI: 10.1016/j.stemcr.2019.10.008
Access URL: https://doaj.org/article/e1fe541275fa4a6b95818095797907a1
Accession Number: edsdoj.1fe541275fa4a6b95818095797907a1
Database: Directory of Open Access Journals
More Details
ISSN:22136711
DOI:10.1016/j.stemcr.2019.10.008
Published in:Stem Cell Reports
Language:English