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PMID: 11559894 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of neurotrophin-induced axonal responses via Rho GTPases.

The Journal of comparative neurology ·Vol. 438 ·No. 4 ·2001-10-01 ·Pages 377-87

Ozdinler PH, Erzurumlu RS

Abstract

Nerve growth factor (NGF) and related neurotrophins induce differential axon growth patterns from embryonic sensory neurons (Lentz et al. [1999] J. Neurosci. 19:1038-1048; Ulupinar et al. [2000a] J. Comp. Neurol 425:622-630). In wholemount explant cultures of embryonic rat trigeminal ganglion and brainstem or in dissociated cell cultures of the trigeminal ganglion, exogenous supply of NGF leads to axonal elongation, whereas neurotrophin-3 (NT-3) treatment leads to short branching and arborization (Ulupinar et al. [2000a] J. Comp. Neurol. 425:622-630). Axonal responses to neurotrophins might be mediated via the Rho GTPases. To investigate this possibility, we prepared wholemount trigeminal pathway cultures from E15 rats. We infected the ganglia with recombinant vaccinia viruses that express GFP-tagged dominant negative Rac, Rho, or constitutively active Rac or treated the cultures with lysophosphatitic acid (LPA) to activate Rho. We then examined axonal responses to NGF by use of the lipophilic tracer DiI. Rac activity induced longer axonal growth from the central trigeminal tract, whereas the dominant negative construct of Rac eliminated NGF-induced axon outgrowth. Rho activity also significantly reduced, and the Rho dominant negative construct increased, axon growth from the trigeminal tract. Similar alterations in axonal responses to NT-3 and brain-derived neurotrophic factor were also noted. Our results demonstrate that Rho GTPases play a major role in neurotrophin-induced axonal differentiation of embryonic trigeminal axons.

MeSH Terms
Afferent Pathways/drug effects,embryology,enzymology Animals Brain-Derived Neurotrophic Factor/metabolism,pharmacology Carbocyanines/pharmacokinetics Cell Differentiation/drug effects,physiology Cell Size/drug effects,physiology Fetus Fluorescent Dyes/pharmacology Gene Expression Regulation, Developmental/drug effects,physiology Genetic Vectors/physiology Growth Cones/drug effects,enzymology,ultrastructure Immunohistochemistry Lysophospholipids/pharmacology Nerve Growth Factor/metabolism,pharmacology Nerve Growth Factors/metabolism,pharmacology Neurons, Afferent/cytology,drug effects,enzymology Neurotrophin 3/metabolism,pharmacology Rats Rats, Sprague-Dawley Transfection Trigeminal Ganglion/drug effects,embryology,enzymology Trigeminal Nuclei/drug effects,embryology,enzymology Vaccinia virus/genetics rac GTP-Binding Proteins/drug effects,genetics,metabolism rho GTP-Binding Proteins/drug effects,genetics,metabolism
Chemicals
3,3'-dihexadecylindocarbocyanine Brain-Derived Neurotrophic Factor Carbocyanines Fluorescent Dyes Lysophospholipids Nerve Growth Factors Neurotrophin 3 Nerve Growth Factor rac GTP-Binding Proteins rho GTP-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ozdinler P H
Department of Cell Biology and Anatomy, LSUHSC, New Orleans, Louisiana 70112, USA.
Erzurumlu R S
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Article Info
Journal
The Journal of comparative neurology
Abbr.
J Comp Neurol
ISSN
0021-9967
DOI
10.1002/cne.1321
Published
2001-10-01
Pages
377-87
Language
English
Region
United States
NLM ID
0406041
PMCID
PMC4260811
Subset
IM
Grants
NIDCR NIH HHS · P01 DE007734 · United States
NINDS NIH HHS · P01 NS049048 · United States
NIDCR NIH HHS · DE07734 · United States
External Links
PubMed source DOI: 10.1002/cne.1321 PMC Full Text View journal details
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