IGF-I specifically enhances axon outgrowth of corticospinal motor neurons

P. Hande Özdinler, Jeffrey D. Macklis*

*Corresponding author for this work

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

Corticospinal motor neurons (CSMN) are among the most complex CNS neurons; they control voluntary motor function and are prototypical projection neurons. In amyotrophic lateral sclerosis (ALS), both spinal motor neurons and CSMN degenerate; their damage contributes centrally to the loss of motor function in spinal cord injury. Direct investigation of CSMN is severely limited by inaccessibility in the heterogeneous cortex. Here, using new CSMN purification and culture approaches, and in vivo analyses, we report that insulin-like growth factor-1 (IGF-I) specifically enhances the extent and rate of murine CSMN axon outgrowth, mediated via the IGF-I receptor and downstream signaling pathways; this is distinct from IGF-I support of neuronal survival. In contrast, brain-derived neurotrophic factor (BDNF) enhances branching and arborization, but not axon outgrowth. These experiments define specific controls over directed differentiation of CSMN, indicate a distinct role of IGF-I in CSMN axon outgrowth during development, and might enable control over CSMN derived from neural precursors.

Original languageEnglish (US)
Pages (from-to)1371-1381
Number of pages11
JournalNature Neuroscience
Volume9
Issue number11
DOIs
StatePublished - Nov 1 2006

ASJC Scopus subject areas

  • Neuroscience(all)

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