case western reserve university





Charles E. Maier, Ph.D.

Regulation of Glia Cell Patterns in the Spinal Cord During Development and Regeneration

Two types of macroglial cells are found in the spinal cord – oligodendrocytes and astrocytes. Oligodendrocytes are the myelinating cells of the vertebrate CNS while astrocytes perform a variety of support functions. The notochord, a transient structure present during development in higher vertebrates, has been shown to produce a protein encoded by the sonic hedgehog gene that regulates motorneuron pattern in mouse, chick and Xenopus. We have found that elimination of the notochord prevents the appearance of differentiated oligodendrocytes while an ectopically implanted notochord is associated with detection of oligodendrocytes in the lateral and dorsal spinal cord at a stage when they should only be found in the ventral spinal cord. Current efforts are directed towards determining whether the appearance and distribution of oligodendrocytes and sonic hedgehog are colocalized. If they do colocalize it would suggest that sonic hedgehog also is the mechanism that regulates oligodendrocyte development. Radial glia, an early stage of astrocyte development, extend from the central canal to the pial surface of the developing spinal cord and are believed to guide growing axons to their targets. The ventrally located notochord seems an unlikely candidate to regulate the pattern of the evenly distributed radial glia/astrocytes. Preliminary studies indicate, however, that the radial glia/astrocyte pattern is altered in the absence of the notochord. Further, Xenopus are capable of regenerating lesioned spinal cord axons until metamorphosis when they lose this ability. Preliminary studies have shown that after the spinal cord is lesioned during development oligodendrocyte and radial glia/astrocyte patterns are perturbed. Studies are currently underway to determine whether the changes in glia cell patterns after spinal cord lesioning may be a response which enables or facilitates the regeneration process. Additional studies are being undertaken to establish whether the notochord, which disappears by metamorphosis, is required for naturally occurring spinal cord regeneration.

Selected References:

Maier C.E., and Miller R.H. Glial cell development and regional specialization in Xenopus spinal cord. Soc. Neurosci. Abstr. Vol. 17, Part 1, p. 733, 1991.

Maier C.E., and Miller R.H. Influence of notochord and surrounding tissue on oligodendrocyte differentiation in Xenopus spinal cord. Soc. Neurosci. Abstr. Vol. 19 Part 2, p. 1712, 1993.

Maier C.E., and Miller R.H. Development of glial cytoarchitecture in the frog spinal cord. Dev. Neurosci. 17:149-159, 1995.

Maier C.E., and Miller R.H. Alteration of radial glia pattern in spinal cords of notochordless Xenopus. Soc. Neurosci. Abstr. Vol. 22, Part 2, p 900, 1996.

Maier C.E., and Miller, R.H. Notochord is essential for oligodendrocyte development. J. Neurosci. Res. 47:361-371, 1997.

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