Molecular heterogeneity of progenitors and radial migration in the developing cerebral cortex revealed by transgene expression.

We have analyzed the developmental pattern of beta-galactosidase (beta-gal) expression in the cerebral cortex of the beta 2nZ3'1 transgenic mouse line, which was generated using regulatory elements of the beta 2-microglobulin gene and shows ectopic expression in nervous tissue. From embryonic day 10 onward, beta-gal was expressed in the medial and dorsal cortices, including the hippocampal region, whereas lateral cortical areas were devoid of labeling. During the period of cortical neurogenesis (embryonic days 11-17), beta-gal was expressed by selective precursors in the proliferative ventricular zone of the neocortex and hippocampus, as well as by a number of migrating and postmigratory neurons arranged into narrow radial stripes above the labeled progenitors. Thus, the transgene labels a subset of cortical progenitors and their progeny. Postnatally, radial clusters of beta-gal-positive neurons were discernible until postpartum day 10. At this age, the clusters were 250 to 500 microns wide, composed of neurons spanning all the cortical layers and exhibiting several neuronal phenotypes. These data suggest molecular heterogeneity of cortical progenitors and of the cohorts of postmitotic neurons originating from them, which implies intrinsic molecular mosaicism in both cortical progenitors and developing neurons. Furthermore, the data show that neurons committed to the expression of the transgene migrate along very narrow, radial stripes.

Radial and tangential dispersion patterns in the mouse retina are cell-class specific.

The retina is derived from a pseudostratified germinal zone in which the relative position of a progenitor cell is believed to determine the position of the progeny aligned in the radial axis. Such a developmental mechanism would ensure that radial arrays of cells which comprise functional units in the mature central nervous system are also clonally related. The present study has tested this hypothesis by using X chromosome-inactivation transgenic mosaic mice. We report that the retina shows a conspicuous distinction for clonally related neuroblasts of different laminar and functional fates: the rod photoreceptor, Müller, and bipolar cells are aligned in the radial axis, whereas the cone photoreceptor, horizontal, amacrine, and ganglion cells are tangentially displaced with respect to them. These results indicate that the dispersion of cell classes across the retinal surface is differentially constrained. Some classes of retinal neuroblast exhibit a significant tangential, as well as radial, component in their dispersion from the germinal zone, whereas others disperse only in the radial dimension. Consequently, the majority of radial columns within the mature retina must be derived from multiple progenitors. Because the cone photoreceptor, horizontal, amacrine, and ganglion cells establish nonrandom matrices in their cellular distributions within the respective retinal layers, tangential dispersion may be the means by which these matrices are constructed.