PMID- 17057708 OWN - NLM STAT- MEDLINE DCOM- 20061219 LR - 20220309 IS - 1097-6256 (Print) IS - 1097-6256 (Linking) VI - 9 IP - 11 DP - 2006 Nov TI - IGF-I specifically enhances axon outgrowth of corticospinal motor neurons. PG - 1371-81 AB - 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. FAU - Ozdinler, P Hande AU - Ozdinler PH AD - MGH-HMS Center for Nervous System Repair, Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. FAU - Macklis, Jeffrey D AU - Macklis JD LA - eng GR - NS41590/NS/NINDS NIH HHS/United States GR - NS45523/NS/NINDS NIH HHS/United States GR - NS49553/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20061022 PL - United States TA - Nat Neurosci JT - Nature neuroscience JID - 9809671 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) SB - IM CIN - Nat Neurosci. 2006 Nov;9(11):1357. PMID: 17066065 MH - Animals MH - Axons/*physiology MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Proliferation/drug effects MH - Cell Separation MH - Cell Size MH - Cell Survival/physiology MH - Flow Cytometry MH - Insulin-Like Growth Factor I/*physiology MH - Mice MH - Motor Neurons/*physiology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Pyramidal Tracts/cytology/*physiology MH - Signal Transduction/drug effects/physiology EDAT- 2006/10/24 09:00 MHDA- 2006/12/21 09:00 CRDT- 2006/10/24 09:00 PHST- 2006/08/21 00:00 [received] PHST- 2006/09/25 00:00 [accepted] PHST- 2006/10/24 09:00 [pubmed] PHST- 2006/12/21 09:00 [medline] PHST- 2006/10/24 09:00 [entrez] AID - nn1789 [pii] AID - 10.1038/nn1789 [doi] PST - ppublish SO - Nat Neurosci. 2006 Nov;9(11):1371-81. doi: 10.1038/nn1789. Epub 2006 Oct 22.