title: Galectin-4, a novel neuronal regulator of myelination.
abstract: Myelination of axons by oligodendrocytes (OLGs) is essential for proper saltatory nerve conduction, i.e., rapid transmission of nerve impulses. Among others, extracellular matrix (ECM) molecules, neuronal signaling, and axonal adhesion regulate the biogenesis and maintenance of myelin membranes, driven by polarized transport of myelin-specific proteins and lipids. Galectin-4, a tandem-repeat-type lectin with affinity to sulfatide and nonsialylated termini of N-glycans, has the ability to regulate adhesion of cells to ECM components and is also involved in polarized membrane trafficking. We, therefore, anticipated that galectin-4 might play a role in myelination. Here, we show that in developing postnatal rat brains galectin-4 expression is downregulated just before the onset of myelination. Intriguingly, when immature OLGs were treated with galectin-4, OLG maturation was retarded, while a subset of the immature OLGs reverted to a morphologically less complex progenitor stage, displaying concomitantly an increase in proliferation. Similarly, myelination was inhibited when galectin-4 or anti-galectin-4 antibodies were added to co-cultures of dorsal root ganglion neurons and OLGs. Neurons and OLGs were identified as a possible source of galectin-4, both in vitro and in vivo. In culture, neurons but not OLGs released galectin-4. Interestingly, in co-cultures, a reduced release of endogenous galectin-4 correlated with the onset of myelination. Moreover, galectin-4-reactive sites are transiently expressed on processes of premyelinating primary OLGs, but not on neurons. Taken together, these results identify neuronal galectin-4 as a candidate for a soluble regulator of OLG differentiation and, hence, myelination. © 2012 Wiley Periodicals, Inc.
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stancic
authors.forename: Davor
authors.initials: D
authors.lastname: Slijepcevic
authors.forename: Anita
authors.initials: A
authors.lastname: Nomden
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Vos
authors.forename: Jenny C
authors.initials: JC
authors.lastname: de Jonge
authors.forename: Arend H
authors.initials: AH
authors.lastname: Sikkema
authors.forename: Hans-J
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000166:cytology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D037541:Galectin 4 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology; D005732:Gangliosides / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D004676:Myelin Basic Protein / Q000502:physiology; D009185:Myelin Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009836:Oligodendroglia; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014161:Transduction, Genetic
chemical_list: D000906:Antibodies; D037541:Galectin 4; D005732:Gangliosides; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D011994:Recombinant Proteins; C062875:ganglioside A2B5; D007770:L-Lactate Dehydrogenase; D001973:Bromodeoxyuridine