C. L. Cepko

We describe a cell-lineage marking system applicable to the vertebrate nervous system. The basis of the technique is gene transfer using the retroviral vector system. We used Escherichia coli beta-galactosidase as a marker gene and demonstrate a high level of expression of this marker from the viral long terminal repeat promoter, with simultaneous expression of the Tn5 neo gene from the simian virus 40 early promoter. This expression has allowed us to detect individual infected cells histochemically. We applied this marking technique to the study of lineage relationships in the developing vertebrate nervous system, both in vivo and in culture. In the rat retina, we injected virus in vivo and histochemically identified clones of marked neural cells. In addition, we used this virus to infect cultures of rat cerebral cortex and have analyzed the clonal relationships of morphologically different neural cell types. The host range of the marking system extends to avian as well as mammalian species. Thus, this system should have broad applicability as a means of gene transfer and expression in the nervous system.

The mammalian cerebral cortex is organized into columns of cells with common functional properties. During embryogenesis, cortical neurons are formed deep, near the lateral ventricles, and migrate radially to their final position. This observation led to the suggestion that the cortex consists of radial, ontogenetic units of clonally related neurons. In the experiments reported here, this hypothesis was tested by studying cell lineage in the rat cortex with a retroviral vector carrying the Escherichia coli beta-galactosidase gene, which can be easily visualized. Labeled, clonally related cortical neurons did not occur in simple columnar arrays. Instead, clonally related neurons entered several different radial columns, apparently by migrating along different radial glial fibers.

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More