title: Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro.
abstract: Myelinating Schwann cells express distinct sensory and motor phenotypes as defined by their differing patterns of growth factor production (Hoke et al., 2006). The heterogeneous growth factor requirements of sensory and motor neurons, however, suggest that Schwann cell phenotype might vary across a broad spectrum. To explore this possibility, we selectively denervated six discrete Schwann cell populations: dorsal root, cutaneous nerve, cutaneous unmyelinated axons, muscle nerve afferents, muscle nerve efferents, and ventral root. Real-time RT-PCR for 11 growth factors was performed on the 6 target Schwann cell populations 5, 15, and 30 days after their denervation, and on normal cutaneous nerve, muscle nerve, ventral root, and dorsal root to establish baseline expression levels. Within the denervated axon populations, IGF-1 and VEGF were expressed most prominently in cutaneous nerve, HGF, NGF, and BDNF in cutaneous nerve and dorsal root, GDNF in dorsal root and ventral root, PTN in the ventral root and muscle nerve efferents, and IGF-2 in both afferents and efferents within muscle nerve; expression of CNTF, FGF-2 and NT-3 was not modality or location specific. ELISA for NGF, BDNF, and GDNF confirmed that gene expression correlated with protein concentration. These findings demonstrate that growth factor expression by denervated Schwann cells is not only subject to further regulation within the previously-defined sensory and motor groups, but also varies along a central-peripheral axis. The traditional view of myelinating Schwann cells as a homogenous population is modified by the realization that complex regulation produces a wide variety of Schwann cell phenotypes. Additionally, we found that Schwann cell phenotype is maintained for 2 weeks in vitro, demonstrating that it may survive several cell divisions without instructive cues from either axons or basal lamina.
authors.affiliation: Johns Hopkins Dept of Orthopaedics, 601N. Caroline St., Baltimore, MD 21287, USA. tbrusha@jhmi.edu
authors.forename: T M
authors.initials: TM
authors.lastname: Brushart
authors.forename: M
authors.initials: M
authors.lastname: Aspalter
authors.forename: J W
authors.initials: JW
authors.lastname: Griffin
authors.forename: R
authors.initials: R
authors.lastname: Redett
authors.forename: H
authors.initials: H
authors.lastname: Hameed
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.forename: A
authors.initials: A
authors.lastname: Vyas
authors.forename: A
authors.initials: A
authors.lastname: Höke
mesh_terms: D000818:Animals; D017763:Autonomic Denervation; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation; D046529:Microscopy, Electron, Transmission; D009414:Nerve Growth Factors / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D012867:Skin / Q000294:innervation; D013997:Time Factors
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger
keywords: BDNF; Brain derived neurotrophic factor; CNTF; Denervation; FGF-2; GDNF; Glial derived neurotrophic factor; HGF; Hepatocyte growth factor; IGF-1; IGF-2; Insulin-like growth factor; NGF; NT-3; Nerve growth factor; PTN; Peripheral nerve; Pleitrophin; VEGF; Vascular endothelial growth factor; brain derived neurotrophic factor; ciliary neurotrophic factor; fibroblast growth factor 2; glial cell line derived neurotrophic factor; hepatocyte growth factor; insulin-like growth factor 1; insulin-like growth factor 2; nerve growth factor; neurotrophin 3; pleiotrophin; vascular endothelial growth factor