Neuregulin-1 type III knockout mice exhibit delayed migration of Schwann cell precursors.
In an embryonic developmental stage of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations. After birth, they eventually wrap around individual axons to form myelin sheaths, which insulate axons to increase the nerve conduction velocity. Some growth factors and adhesion molecules are known to control these developmental stages from in the fish to in the mammal. Neuregulin-1 (NRG1), which is composed of many alternative splicing variants, is such a growth factor. Among these variants, the type III isoform of NRG1, interacting with ErbB2 and ErbB3 receptors on Schwann cells, plays an essential role in myelination in the fish and the mammal. NRG1 type III is also known to promote migration of fish Schwann cell precursors; however, it still remains to be clarified whether mammalian type III isoform does it. We have therefore generated type III isoform-specific knockout mice in inbred strain. The mice result in delayed migration of the precursors from the dorsal to ventral root via a peripheral ganglion, comparing littermate controls. Similar results are observed in an in vitro migration assay using reaggregated Schwann cell precursors. Furthermore, the knockout mice exhibit reduced myelin thickness, consistent with the established role of NRG1 type III in myelination. These results indicate that in mice, NRG1 type III plays a key role not only in myelination but also in migration.
Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
Yuki
Y
Miyamoto
Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
Tomohiro
T
Torii
Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
Akito
A
Tanoue
Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
Kazuko
K
Kawahara
Experimental Animal Faculty, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
Miyuki
M
Arai
Experimental Animal Faculty, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
Hideki
H
Tsumura
Department of Rehabilitation for the Movement Functions, National Rehabilitation Center for Persons with Disabilities Research Institute, Tokorozawa, Saitama 359-8555, Japan.
Toru
T
Ogata
Department of Rehabilitation for the Movement Functions, National Rehabilitation Center for Persons with Disabilities Research Institute, Tokorozawa, Saitama 359-8555, Japan.
Motoshi
M
Nagao
Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
Nobuo
N
Terada
Tsumura Research Laboratories, Tsumura & Co., Inashiki, Ibaraki 200-1192, Japan.
Masahiro
M
Yamamoto
Glycobiology Research Unit, The Noguchi Institute, Itabashi, Tokyo 173-0003, Japan.
Shou
S
Takashima
Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan. Electronic address: yamauchi@toyaku.ac.jp.
Junji
J
Yamauchi
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C490581:Nrg1 protein, mouse; C000607800:ErbB3 protein, mouse
Knockout mouse; Migration; Neuregulin-1 type III; Schwann cell precursor