Mechanisms of neuronal localization in the developing brain

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Cerebral cortical neurons form a six-layered structure in which their position depends on their birth-date. This developmental process requires the presence of Reelin, which is secreted by Cajal-Retzius cells in the cortical marginal zone (MZ). However, it is still unclear whether the migration from the ventricular zone (VZ) to beneath the MZ is essential for the projection neurons to segregate into layers. Previous transplantation studies of ferret cerebral cortical neurons suggested that their ultimate laminar fate is, at least to some extent, determined in the VZ, but it is unknown how "laminar fate" eventually positions cell in a specific layer. To explore the segregation properties of cortical cells that have not yet arrived beneath the MZ, embryonic day (E) 16 VZ and intermediate zone (IMZ) cells were dissociated and allowed to reaggregate for 1-4 days in vitro. The result suggested that the migrating neurons in the IMZ at E16 preferentially located near the center of the aggrega … More tes more than the proliferative cells in the VZ. The birth-date-labeling followed by the dissociation/reaggregation culture suggested that the segregation properties of the E16 IMZ was characteristic of the E14-born cells, which were migrating in the IMZ at E16, but they were not general properties of migrating IMZ cells. This birth-date-dependent segregation mechanism was also observed in the Reelin-signaling-deficient yotari cells. These findings suggest that cortical neurons acquire a birth-date-dependent segregation mechanism before their somas reach the MZ. In contrast to the projection neurons described above, gamma-aminobutyric acid (GABA)ergic interneurons arise in the ventral telencephalon and migrate into the cortical plate tangentially. Although the "inside-out" alignment of projection neurons in the cortex has been thoroughly analyzed, the pattern of interneuron alignment is not well understood. In this study, we show that in the postnatal day (P) 9.5 mouse visual cortex, GABAergic neurons born on embryonic day (E) 12.5 were distributed around two peak locations, mainly around layer V and also around layer II/III, while non-GABAergic neurons born on E12.5 were distributed around only one peak in layer VI. Both cell populations born on E15.5 exhibited only one common peak distribution in layer II/III. The two peak locations of GABAergic neurons born on E12.5 still existed at P30. When the subtypes of GABAergic neurons were analyzed, calretinin-positive cells born on E12.5 were distributed in the cortex around one peak location near layer II/III, whereas somatostatin-positive E12.5 cells were distributed in the cortex around one peak location near layer V. These results suggest that the alignment of interneurons is regulated differently according to subtypes and from that of projection neurons having the same embryonic day of origin. Less