Neurons and glial cells of the embryonic human brain and spinal cord express multiple and distinct isoforms of laminin

Liesi, Päivi; Fried, Gabriel; Stewart, Randall R.

doi:10.1002/jnr.1061

Cited by 47 publications

(64 citation statements)

References 61 publications

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“…Of these ligands, however, only laminins have been shown to play a role in regulating CNS myelination to date, and we suggest that the dysmyelination associated with laminin deficiency is likely to involve the disruption of at least two classes of receptor interactions: integrin and DG. Laminin ␣2 expression has been reported in the early stages of myelinating white matter tracts, yet it remains unclear how oligodendrocytes interact with this transient CNS laminin (Anderson et al, 2005;Colognato et al, 2002;Farwell and DubordTomasetti, 1999;Georges-Labouesse et al, 1998;Hagg et al, 1997;Liesi et al, 2001;Morissette and Carbonetto, 1995;Powell et al, 1998;Tian et al, 1997). One possibility is that CNS ␣2-laminins help to regulate axonal-glial interactions at early stages of axon ensheathment, when instructive cues for survival and/or differentiation are needed.…”

Section: Discussionmentioning

confidence: 99%

Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination

et al. 2007

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2Developmental abnormalities of myelination are observed in the brains of laminin-deficient humans and mice. The mechanisms by which these defects occur remain unknown. It has been proposed that, given their central role in mediating extracellular matrix (ECM) interactions, integrin receptors are likely to be involved. However, it is a non-integrin ECM receptor, dystroglycan, that provides the key linkage between the dystrophin-glycoprotein complex (DGC) and laminin in skeletal muscle basal lamina, such that disruption of this bridge results in muscular dystrophy. In addition, the loss of dystroglycan from Schwann cells causes myelin instability and disorganization of the nodes of Ranvier. To date, it is unknown whether dystroglycan plays a role during central nervous system (CNS) myelination. Here, we report that the myelinating glia of the CNS, oligodendrocytes, express and use dystroglycan receptors to regulate myelin formation. In the absence of normal dystroglycan expression, primary oligodendrocytes showed substantial deficits in their ability to differentiate and to produce normal levels of myelin-specific proteins. After blocking the function of dystroglycan receptors, oligodendrocytes failed both to produce complex myelin membrane sheets and to initiate myelinating segments when co-cultured with dorsal root ganglion neurons. By contrast, enhanced oligodendrocyte survival in response to the ECM, in conjunction with growth factors, was dependent on interactions with beta-1 integrins and did not require dystroglycan. Together, these results indicate that laminins are likely to regulate CNS myelination by interacting with both integrin receptors and dystroglycan receptors, and that oligodendrocyte dystroglycan receptors may have a specific role in regulating terminal stages of myelination, such as myelin membrane production, growth, or stability.

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Section: Discussionmentioning

confidence: 99%

Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination

et al. 2007

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“…It is less clear, however, whether neurons also express laminin genes. In fact, many groups have reported that laminins are present in neuropil and neurons of the mammalian brain (Letourneau et al, 1988;Yamamoto et al, 1988Yamamoto et al, , 1997Gordon-Weeks et al, 1989;Hagg et al, 1989Hagg et al, , 1997Hunter et al, 1992;Liesi et al, 1995Liesi et al, ,2001Morissette and Carbonetto, 1995;Tian et al, 1997;Raabe et al, 1997;Lentz et al, 1997;Chen and Strickland, 1997;Sewry et al, 1998;Powell et al, 1998;Nakagami et al, 2000;Libby et al, 2000;Palu and Liesi, 2002;Murase and Horwitz, 2002). However, there is little consensus on the forms present and their localization.…”

Section: Introductionmentioning

confidence: 92%

Expression of laminin chains by central neurons: Analysis with gene and protein trapping techniques

Yin

Kikkawa

Mudd

et al. 2003

Genesis

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Laminins exert numerous effects on neurons in vitro, but expression of laminin subunit genes by neurons in vivo remains controversial. To reexamine this issue, we generated mice from ES cells in which the laminin alpha1, alpha5, beta1, and gamma1 genes had been "trapped" by insertion of a histochemically detectable selectable marker, betageo (beta-galactosidase fused to neomycin phosphotransferase). The presence of laminin-betageo fusion proteins was assayed histochemically and immunochemically, revealing expression of laminin beta1 and gamma1 genes, but not alpha chain genes, by defined subsets of neurons in brain and retina. We also used the gene traps in a novel way to assay expression of endogenous laminin subunits, which were barely detectable by ordinary immunohistochemical methods. The trapping vector included a transmembrane domain that anchors proteins otherwise destined for secretion. Laminin alpha/beta/gamma heterotrimers are assembled intracellularly, and we show that the trapped laminin gamma1 fusion protein "co-trapped" endogenous beta1 intracellularly. The laminin gamma1 fusion was also able to co-trap transgene-derived alpha chains, but we detected no co-trapped endogenous alpha chains. The co-trapping method may be generally useful for identifying proteins or isolating protein complexes associated with trapped gene products.

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“…Primary neuronal cultures from whole brains of similarly aged adult mice were prepared by a modification of the method of Liesi et al [23]. After removal of the meninges, each brain was triturated in serum-free Modified Eagle Medium (MEM) approximately 20 times, and the solid tissue was allowed to settle and thereby separate from the partially dissociated cells in the supernatant.…”

Section: Primary Cellsmentioning

confidence: 99%

Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy

Boeras

Granic

Padmanabhan

et al. 2008

Neurobiology of Aging

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Mutations in the presenilin 1 gene cause most early-onset familial Alzheimer's disease (FAD). Here we report that a defect in the cell cycle-improper chromosome segregation-can be caused by abnormal presenilin function and therefore may contribute to AD pathogenesis. Specifically we find that either over-expression or FAD mutation in presenilin 1 (M146L and M146V) leads to chromosome missegregation and aneuploidy in vivo and in vitro: 1) Up to 20% of lymphocytes and neurons of FAD-PS-1 transgenic and knockin mice are aneuploid by metaphase chromosome analysis and in situ hybridization, 2) Transiently transfected human cells over-expressing normal or mutant PS-1 develop similar aneuploidy within 48 hours, including trisomy 21. 3) Mitotic spindles in the PS-1 transfected cells contain abnormal microtubule arrays and lagging chromosomes. Several mechanisms by which chromosome missegregation induced by presenilin may contribute to Alzheimer's disease are discussed.

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Neurons and glial cells of the embryonic human brain and spinal cord express multiple and distinct isoforms of laminin

Cited by 47 publications

References 61 publications

Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination

Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination

Expression of laminin chains by central neurons: Analysis with gene and protein trapping techniques

Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy

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