Udo Bartsch

Zentrum fuer Molekulare Neurobiologie, Universitaet Hamburg, Martinistr. 52, D-20246 Hamburg, Germany

FIGURES

Figure 2. Ultrastructural abnormalities of myelin sheaths in the optic nerves of MAG null mutant mice. Compact myelin in the optic nerve of MAG-deficient mice displays a normal ultrastructure (a, b), and axons and myelin sheaths are separated by a periaxonal space of normal width (arrowheads in a). Note, however, that most myelin sheaths lack a well-developed periaxonal cytoplasmic collar (a, b). Note also the presence of doubly myelinated axons (labeled with ax in a and b). The inner myelin sheaths (labeled with a single asterisk in a and b) are spiraling clockwise, whereas the outer myelin sheaths (labeled with a pair of asterisks in a and b) are spiraling counterclockwise. The outer tongue process of the inner and outer myelin sheath in (a) is labeled with (1) and (2), respectively. Ax, axon. Bar in (a): 0.2 µm; in (b): 0.5 µm. Reproduced with modifications from (85).

Figure 3. Dying-back oligodendrogliopathy in the optic nerve of MAG-deficient mice. Degenerative alterations of distal oligodendrocyte processes start within compact myelin (a) or periaxonally (b, c) and are characterized by the presence of membraneous inclusions, vesicles and osmiophilic material. Note the normal ultrastructure of corresponding axons. Note also the presence of redundant myelin (labeled with white dots in a-c). A, axon. Bars (in a-c): 0.5 µm. Reproduced with modifications from (33).

Figure 4. Myelination of dorsal root ganglion neurons by MAG-deficient Schwann cells in vitro. MAG-deficient Schwann cells form morphologically intact myelin sheaths around neurites of co-cultured dorsal root ganglion neurons, with a normal periodicity of major dense and intraperiod lines and a well developed periaxonal Schwann cell cytoplasmic collar (arrows). Note that the myelin sheath and the axon are separated by a periaxonal space of normal width (arrowheads). Bar: 0.2 µm. Reproduced from (33).

Figure 5. Pathological alterations in peripheral nerves of MAG/NCAM double mutant mice.A relatively small axon surrounded by thick myelin (m) in the quadriceps nerve of a one-month-old MAG/NCAM mutant (a). Note the densely packed neurofilaments within the axon (a). (b) An onion bulb formation in the quadriceps nerve of a 26-week-old MAG/NCAM mutant consisting of an axon that is surrounded by a relatively thin myelin sheath and supernumerous Schwann cells (arrows). m, myelin tomaculum; M, myelin. Bar (in a): 2 µm; (in b): 1 µm. Reproduced from (100).

Figure 6. The percentage of unmyelinated axons in the optic nerves of mice with different genotypes.The percentage of unmyelinated axons was determined in optic nerves of two- (a) and nine-month-old (b) wild-type (open bars), MAG- (hatched bars), Fyn- (grey bars) and MAG/Fyn- (filled bars) deficient mice. Note the similar values for each genotype at both developmental ages. Note also that the percentage of unmyelinated axons in optic nerves of MAG/Fyn double mutants is significantly increased when compared to Fyn mutants (p < 0.0001 according to the unpaired t test). Each bar represents the mean value ±SD from six animals. Reproduced with modifications from (120).

Figure 7. Normal numbers of oligodendrocytes in optic nerves of MAG/Fyn-deficient mice. (A) Oligodendrocytes were visualized in cross-sectioned optic nerves from adult wild-type (a-c) and MAG/Fyn-deficient (d-f) mice by in situ hybridization using cRNA probes specific to proteolipid protein/DM-20 (a,d), proteolipid protein (b,e) and myelin oligodendrocyte glycoprotein (c,f). Note the similar numbers of labeled cells in optic nerves of both genotypes. (B) Quantitative analysis confirmed the presence of similar numbers of proteolipid protein-positive oligodendrocytes in wild-type (open bar) and MAG/Fyn-deficient (filled bar) optic nerves. Each bar represents the mean value ±SD from six animals. (ns: not significantly different according to the unpaired t test).

Figure 8. MAG, but not Fyn is essential for the formation of normal myelin sheaths in the CNS. Myelin sheaths in the optic nerve of adult MAG/Fyn-deficient mice (a) lack a well developed periaxonal cytoplasmic collar, and some sheaths elaborate redundant myelin (white dots in a) or display degenerative alterations (large asterisk in a). Note the presence of numerous unmyelinated and small-sized axons in the MAG/Fyn-deficient optic nerve (some labeled with small asterisks in a). Myelin sheaths in the optic nerve of adult Fyn mutants (b), in contrast, display a normal morphology with a well developed periaxonal cytoplasmic collar (arrowheads in b). Note that many axons are unmyelinated and of small caliber (some labeled with asterisks in b). Ax, axon; M, myelin. Bar in (b): 0.5 µm for (a); 0.25 µm for (b). Reproduced from (120).

Figure 9. Pathological alterations in peripheral nerves of L1-deficient mice are confined to unmyelinated fibers. Each myelinating Schwann cell (mSC) in peripheral nerves of wild-type mice (a) engages with a single axon (ax) and forms a single internodal myelin segment. Nonmyelinating Schwann cells (nSC) ensheath several unmyelinated axons in separate cytoplasmic troughs (a). Note that most unmyelinated axons in wild-type nerves (some labeled with asterisks in a) are completely surrounded by the Schwann cell. Myelinated fibers in sciatic nerves of two-month-old L1-deficient mice (b) display a normal morphology. Note, however, the low number of axons associated with one nonmyelinating Schwann cell (nSC in b). Note also the redundant processes of the nonmyelinating Schwann cell (arrowheads in b) and the presence of axons (labeled with asterisks in b) that are only incompletely ensheathed by Schwann cell processes. M, myelin. Bar in (a): 2 µm; in (b): 1 µm.