Early regionalisation of the neocortex and the medial ganglionic eminence.

The two major functional classes of neurons that build the cerebral cortex are generated in two distinct parts of the telencephalon. Excitatory long distance projecting neurons are produced dorsally in the pallium, whereas local inhibitory interneurons are mainly produced in the medial ridge of the ventral telencephalon. These two parts of the telencephalon are molecularly regionalized from early embryonic stages, but cellular indices of regionalisation are observed only at later stages of development. We have looked for cellular indices of regionalisation in the cortical anlage at early embryonic stages, when the first efferent cortical neurons are generated. Similarly, we have looked for functional regionalisation of the medial ganglionic eminence at the same stages, when the future cortical interneurones are generated. Here, we summarize data showing that two regions in the mouse cortex embryo, the lateral and dorsal cortex, differ strongly in their early neurogenesis. Moreover, the two domains differ in their capacity to produce GABAergic neurons in vitro; this capacity is only observed in the dorsal cortex. The differentiation of the two domains appears to be independent of the laterorostral to mediocaudal gradient of maturation of the cortex. In the basal telencephalon too, the capacity to differentiate GABAergic neurons is not uniformly distributed across the medial ganglionic eminence. The neurogenesis of future cortical interneurons is seen to be highly active in a small area located in the rostral MGE, at mid dorso-ventral level.

Nucleokinesis in tangentially migrating neurons comprises two alternating phases: forward migration of the Golgi/centrosome associated with centrosome splitting and myosin contraction at the rear.

During rodent cortex development, cells born in the medial ganglionic eminence (MGE) of the basal telencephalon reach the embryonic cortex by tangential migration and differentiate as interneurons. Migrating MGE cells exhibit a saltatory progression of the nucleus and continuously extend and retract branches in their neuritic arbor. We have analyzed the migration cycle of these neurons using in vitro models. We show that the nucleokinesis in MGE cells comprises two phases. First, cytoplasmic organelles migrate forward, and second, the nucleus translocates toward these organelles. During the first phase, a large swelling that contains the centrosome and the Golgi apparatus separates from the perinuclear compartment and moves rostrally into the leading neurite, up to 30 mum from the waiting nucleus. This long-distance migration is associated with a splitting of the centrioles that line up along a linear Golgi apparatus. It is followed by the second, dynamic phase of nuclear translocation toward the displaced centrosome and Golgi apparatus. The forward movement of the nucleus is blocked by blebbistatin, a specific inhibitor of nonmuscle myosin II. Because myosin II accumulates at the rear of migrating MGE cells, actomyosin contraction likely plays a prominent role to drive forward translocations of the nucleus toward the centrosome. During this phase of nuclear translocation, the leading growth cone either stops migrating or divides, showing a tight correlation between leading edge movements and nuclear movements.

Early differences in axonal outgrowth, cell migration and GABAergic differentiation properties between the dorsal and lateral cortex.

The regionalization of the cerebral cortex proceeds gradually from early embryonic stages under the control of transcription factors that are expressed in gradients. Two phases can be distinguished at the beginning of cortical development: the genesis of a precocious and transient structure, the preplate, which is followed by development of the cortical plate within the preplate. Cellular indices of early regionalization have not yet been described either in the preplate or in the early cortical plate. In the present study, we identify two regions, lateral and dorsal, in the mouse cortex embryo, which differ strongly in the functional properties of their early neurons. By using culture experiments and grafts on organotypic slices, we show that the earliest neurons in the dorsal cortex extend axons before and more rapidly than the earliest neurons in the lateral cortex. In contrast to the lateral cortex, the dorsal cortex differentiates neurons migrating along axons in vitro. These cells express markers of the GABAergic lineage. Early differences between the two regions suggest that the dorsal part of the cortex generates early neurons with particular intrinsic properties that may in turn specifically influence the later development of the cortical plate in this domain.