Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pure populations of sensory neurons (N), Schwann cells (S) and fibroblasts (Fb) were established in culture from normal and dystrophic (dy) mice in order to investigate the cellular origin(s) of the peripheral nervous system abnormalities present in murine muscular dystrophy. These cell types were placed together in various combinations and their subsequent interactions were monitored with the light and electron microscope. The formation of the basal lamina (BL) which in normal tissue, completely surrounds the external aspect of the Schwann cell (when in contact with axons) was documented by morphometric analysis of electron micrographs. Defects in Schwann cell BL formation, observed throughout the PNS of the dy mouse in vivo, were used as a marker for the expression of the dystrophic abnormality in culture. Initially mature cultures of dy tissues containing only S and N (SN) without Fb were examined and found to contain an incomplete BL that surrounded only 82.8 +/- 12.2% of the externally directed plasmalemma of axon-related Schwann cells. The following recombination cultures were established: (1) normal S were placed on dystrophic N; (2) dystrophic S were placed on dystrophic N; (3) dystrophic S were placed on normal N; and (4) normal Fb were added to a dystrophic SN culture. After a 5-week period, the BL formed by normal S in direct contact with dystrophic N was thick and continuous (97.7 +/- 2.2 coverage). On the other hand, in culture situations (without Fb) containing dystrophic S in contact with either dystrophic or normal neurites, the BL coverage was considerably less (58.5 +/- 14.8% and 55.4 +/- 13.2%, respectively). The addition of normal Fb obtained from sciatic nerve explants to dystrophic SN cultures in time resulted in the formation of a morphologically complete BL (98.9 +/- 1.4% coverage). We conclude that neuronal signal(s) are adequate to induce complete BL formation by Schwann cells in the dystrophic tissue but that dystrophic Schwann cells are incapable of forming a complete BL. Furthermore, this deficiency of dy Schwann cells is apparently corrected by the presence of normal Fb by an unknown mechanism.
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PMID:Factors affecting schwann cell basal lamina formation in cultures of dorsal root ganglia from mice with muscular dystrophy. 715 44

Using specific monoclonal antibodies against different subunits of laminin, we studied the differential distribution pattern of several laminin chains in the central (CNS) and peripheral (PNS) nervous system. Laminin chains alpha 1, beta 1 and gamma 1, were found in the basement membrane (BM) of blood vessels in both CNS and PNS. In contrast, laminin alpha 2 though present in the BM of capillaries in the CNS, was completely absent from PNS capillaries. Laminins alpha 2, beta 1, gamma 1 could be detected in peripheral nerve, in the BM of Schwann cells, which did not contain Laminin alpha 1. The possible importance of laminin alpha 2 for myelination in the PNS as well as in the function of the blood-brain barrier in the CNS, and its potential relevance to the pathology of congenital muscular dystrophy associated with deficiency of this laminin chain, is discussed.
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PMID:Immunolocalization of several laminin chains in the normal human central and peripheral nervous system. 926 51

Myelin is essential for rapid and efficient action potential propagation in vertebrates. However, the molecular mechanisms regulating myelination remain incompletely characterized. For example, even before myelination begins in the PNS, Schwann cells must radially sort axons to form 1:1 associations. Schwann cells then ensheathe and wrap axons, and establish polarized, subcellular domains, including apical and basolateral domains, paranodes, and Schmidt-Lanterman incisures. Intriguingly, polarity proteins, such as Pals1/Mpp5, are highly enriched in some of these domains, suggesting that they may regulate the polarity of Schwann cells and myelination. To test this, we generated mice with Schwann cells and oligodendrocytes that lack Pals1. During early development of the PNS, Pals1-deficient mice had impaired radial sorting of axons, delayed myelination, and reduced nerve conduction velocities. Although myelination and conduction velocities eventually recovered, polyaxonal myelination remained a prominent feature of adult Pals1-deficient nerves. Despite the enrichment of Pals1 at paranodes and incisures of control mice, nodes of Ranvier and paranodes were unaffected in Pals1-deficient mice, although we measured a significant increase in the number of incisures. As in other polarized cells, we found that Pals1 interacts with Par3 and loss of Pals1 reduced levels of Par3 in Schwann cells. In the CNS, loss of Pals1 affected neither myelination nor the establishment of polarized membrane domains. These results demonstrate that Schwann cells and oligodendrocytes use distinct mechanisms to control their polarity, and that radial sorting in the PNS is a key polarization event that requires Pals1. Significance statement: This paper reveals the role of the canonical polarity protein Pals1 in radial sorting of axons by Schwann cells. Radial sorting is essential for efficient and proper myelination and is disrupted in some types of congenital muscular dystrophy.
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PMID:The Polarity Protein Pals1 Regulates Radial Sorting of Axons. 2620 42