Synapse formation is arrested in retinal photoreceptors of the zebrafish nrc mutant.

We describe the effects of a recessive mutation on visual behavior, the electroretinogram (ERG), and photoreceptor structure in zebrafish. At 6 d post-fertilization (dpf), no optokinetic reflex could be elicited in no optokinetic response c (nrc) mutant animals under any test condition. The animals exhibited ERG responses at 5-7 dpf that were markedly abnormal and could be categorized into two groups. The first showed an initial negative a-wave followed by a delayed positive b-wave of small amplitude. Often a second ERG-like response was recorded after the initial b-wave. The second group showed only a large negative a-wave; an initial b-wave was not evident. In most recordings additional oscillatory waves varying in number, amplitude, and time course were observed. Multiple responses at the cessation of long-duration flashes were also observed. Light and electron microscopy revealed that the cone photoreceptor pedicles of nrc fish were highly abnormal. Although the appropriate number of synaptic ribbons formed in these terminals, they "floated" in the terminal, unassociated with postsynaptic processes or arciform densities. The few processes invaginating the nrc pedicles resembled those of horizontal cells. Invaginating bipolar cell processes were rare, but basal contacts were observed on pedicle surfaces. The severity of the mutation did not change between 6 and 8 dpf, showing that there is neither a delay in development nor a degeneration of the terminals; rather, nrc pedicle development appears arrested. Bipolar cell terminals in the inner plexiform layer made normal ribbon synapses; thus, the mutation appears to affect only the outer retina.

The pineal gland in wild-type and two zebrafish mutants with retinal defects.

Light and transmission electron microscopy were used to characterize the ultrastructural features of the pineal glands of wild-type and two mutant zebrafish strains that have retinal defects. Particular attention was given to the pineal photoreceptors. Photoreceptors in the pineal gland appear quite similar to retinal cone photoreceptors, having many of the same structural characteristics including outer segment disk membranes often confluent with the plasma membrane, calycal processes surrounding the outer segments, and classic connecting cilia. The pineal photoreceptor terminals differ from photoreceptor terminals in the retina in that they have short synaptic ribbons and make dyad synapses which may or may not be invaginated. Pineal photoreceptors in two zebrafish mutants with abnormal retinal photoreceptors were also studied. Pineal photoreceptors in the niezerka (nie) mutant degenerate, as they do in the retina, indicating that pineal and retinal photoreceptors share at least some genes. However, the synaptic terminals of no optokinetic response c (nrc) pineal photoreceptors are normal, suggesting that this mutation is specific to the retina.

Expression of the oligodendrocyte-myelin glycoprotein by neurons in the mouse central nervous system.

The oligodendrocyte-myelin glycoprotein (OMgp) is a 110-kDa glycosylphosphatidylinositol-linked protein that was initially identified as a myelin-specific protein but whose precise function remains unknown. In this study, immunohistochemistry, western blots, in situ hybridization, and northern blots were used to determine the distribution of OMgp in the mouse brain. OMgp is present in a concentration detectable on western blots in the brains of newborn mice, and its concentration gradually increases until day 24 of life. OMgp mRNA is also present in amounts detectable on northern blots in the brains of newborn mice, and its concentration gradually increases until day 21 of life, after which the concentration diminishes a little. Most of the OMgp in the mouse brain appears to be expressed in diverse groups of neurons, but it is particularly prominent in large projection neurons such as the pyramidal cells of the hippocampus, the Purkinje cells of the cerebellum, motoneurons in the brainstem, and anterior horn cells of the spinal cord. However, OMgp is not confined to these cells and is expressed in cells in the white matter as well. The OMgp gene is placed within an intron of the neurofibromatosis type I gene and on the opposite strand. This organization raises the possibility that there may be a relationship between the functions of the products of the two genes. In support of this possibility, we show that within the mouse CNS OMgp and neurofibromin are expressed in the same cell types.

The oligodendrocyte-myelin glycoprotein of mouse: primary structure and gene structure.

The oligodendrocyte-myelin glycoprotein (OMgp), a phosphatidylinositol-linked membrane glycoprotein expressed in the brain, is in man encoded by a gene that is entirely within an intron of and on the strand opposite to the neurofibromatosis type 1 (NF1) gene. We obtained two distinct overlapping DNA clones from a mouse genomic library that contain the OMgp gene from mouse (mOMgp). There is a single intron in the 5' untranslated region in exactly the same position as the sole intron in the gene for the human OMgp (hOMgp). A repeat, (TC)24, in the mouse intron divides it into 5' and 3' segments that have 72 and 93% sequence identity, respectively, with the human gene. The deduced unprocessed polypeptides of both species have 440 amino acids and the similarity of the primary structures of mOMgp and hOMgp indicates conservation of function. The conservation of the nucleotide sequences of the coding, noncoding, and flanking regions of the two genes is remarkable and raises the possibility that the nucleotide sequence may serve a function that is separate from the role of encoding OMgp.