Transgenic mice were generated to permit the targeted ablation of cortical preplate cells at the time they are born. In these mice, the 1.3 kb golli promoter of the myelin basic protein gene was used to drive the herpes simplex virus thymidine kinase (TK) transgene in cortical preplate cells. Heterozygous transgenic pairs were bred, and pregnant dams were treated with ganciclovir at embryonic days 11-12 to ablate preplate cells at the time the preplate was forming. This paradigm exposed control (TK-) and experimental (TK+) littermates to exactly the same conditions. Embryological ablation of preplate cells led to an early disruption of the radial glial framework and subplate structure in the developing cortex and dramatically altered the cellular lamination and connectivity of the cortical plate. The disturbed radial glial network contributed to an impaired radial migration of neurons into the cortical plate from the ventricular zone. The cortical plate became dyslaminated, and there was a substantial reduction in short- and long-range cortical projections within the cortex and to subcortical regions. Cell death within the cortical plate and the proliferative zones was substantially increased in the ablated animals. After birth, a cortical lesion developed, which became exacerbated with the secondary onset of hydrocephaly in the second postnatal week. The results underscore the critical importance of the preplate in cortex formation, mediated through its guidance of the formation of radial glial scaffolding, subsequent neuronal migration into the incipient cortical plate, and the final arrangement of its vertical organization and cellular connectivity.
The Golli-myelin basic protein (MBP) transcription unit gives rise to two sets of products. One set (i.e., the MBPs) is expressed exclusively in myelin forming cells and the other set (i.e., the golli isoforms) is expressed in both oligodendrocytes and neurons in the CNS. The two major golli proteins, generated from RNAs transcribed from the most upstream promoter of the gene, contain MBP peptide sequences in their C-terminal halves and are, therefore, structurally and immunologically related to the MBPs. We have examined the distribution and localization of golli proteins in the mouse peripheral nervous system (PNS) using immunocytochemistry with a golli-specific antibody. Golli immunoreactivity was first observed in sensory and motor fibers of the mouse at E11 during fiber tract extension, but prior to the maturation of terminal connections. Once neuromuscular junctions had formed, golli immunoreactivity appeared in motor endplates and persisted to the latest age examined, P60. Golli immunoreactivity was also observed in the cell bodies and processes of the dorsal root ganglia throughout development. Strong staining in the PNS of the dysmyelinating mutant shiverer suggested that the major golli protein in peripheral fibers was the BG21 isoform. Interestingly, golli immunoreactivity was also found in adrenal chromaffin cells, which share a common neural crest derivation with other postganglionic neurons that express golli protein. These results suggest that in addition to its role in early forming neuronal systems of the CNS, golli protein also plays a role in the early development and maintenance of neurons in the PNS.
The Golli-myelin basic protein (MBP) transcription unit gives rise to two sets of products. One set (i.e., the MBPs) is expressed exclusively in myelin forming cells and the other set (i.e., the golli isoforms) is expressed in both oligodendrocytes and neurons in the CNS. The two major golli proteins, generated from RNAs transcribed from the most upstream promoter of the gene, contain MBP peptide sequences in their C-terminal halves and are, therefore, structurally and immunologically related to the MBPs. We have examined the distribution and localization of golli proteins in the mouse peripheral nervous system (PNS) using immunocytochemistry with a golli-specific antibody. Golli immunoreactivity was first observed in sensory and motor fibers of the mouse at E11 during fiber tract extension, but prior to the maturation of terminal connections. Once neuromuscular junctions had formed, golli immunoreactivity appeared in motor endplates and persisted to the latest age examined, P60. Golli immunoreactivity was also observed in the cell bodies and processes of the dorsal root ganglia throughout development. Strong staining in the PNS of the dysmyelinating mutant shiverer suggested that the major golli protein in peripheral fibers was the BG21 isoform. Interestingly, golli immunoreactivity was also found in adrenal chromaffin cells, which share a common neural crest derivation with other postganglionic neurons that express golli protein. These results suggest that in addition to its role in early forming neuronal systems of the CNS, golli protein also plays a role in the early development and maintenance of neurons in the PNS.
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