MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents.
Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo-cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1-related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labelling and anti-MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell-adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth-promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.
Kawauchi
Daisuke
D
Division of Biophysical Engineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
Kobayashi
Hiroaki
H
Sekine-Aizawa
Yoko
Y
Fujita
Shinobu C
SC
Murakami
Fujio
F
D000375:Aging; D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D002232:Carbocyanines / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000033:anatomy & histology / Q000502:physiology*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000378:metabolism; D005207:Fasciculation / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D017950:Ganglia, Sensory / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D016501:Neurites / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology*; D009687:Nuclear Proteins; D012249:Rhombencephalon; D014157:Transcription Factors; D014162:Transfection; D014722:Vestibule, Labyrinth / Q000033:anatomy & histology / Q000502:physiology*
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009687:Nuclear Proteins; C121661:Prdm4 protein, rat; D014157:Transcription Factors; D049452:Green Fluorescent Proteins