Subpallial origin of a population of projecting pioneer neurons during corticogenesis.

Pyramidal neurons of the mammalian cerebral cortex are generated in the ventricular zone of the pallium whereas the subpallium provides the cortex with inhibitory interneurons. The marginal zone contains a subpial stream of migratory interneurons and two different classes of transient neurons, the pioneer neurons provided with corticofugal axons, and the reelin-expressing Cajal-Retzius cells. We found in cultured slices that the medial ganglionic eminence provides the reelin-negative pioneer neurons of the marginal zone. Pioneer neurons sent long projection axons that went through the cortical plate and reached the subplate and the lateral border of the lateral ganglionic eminence. In the cultured slices, pioneer neurons were functionally mature: they displayed a voltage-gated sodium current, expressed functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and showed gamma-aminobutyric acid type A (GABAA) postsynaptic events that were modulated by presynaptic AMPA receptors. Pioneer neurons expressed the adhesion molecules L1 and TAG-1; the latter has been reported to control tangential migrations to the neocortex [Denaxa, M., Chan, C.-H., Schachner, M., Parnavelas, J. & Karagogeos, D. (2001) Development (Cambridge, U.K.) 128, 4635-4644], and we show here that the pioneer neurons of the marginal zone are the cellular substrate of such a function. Finally, we show that, in early corticogenesis, reelin controls both the tangential migration of cortical interneurons toward the cortical plate and the tangential migration of pioneer neurons toward the marginal zone.

Substrates and routes of migration of early generated neurons in the developing rat thalamus.

We investigated the substrates supporting neuronal migration, and its routes, during early thalamic development in the rat. Neurons and axonal and glial fibres were identified in embryos with single and double immunohistochemistry; dynamic data were obtained with cell tracers in short-term organotypic cultured slices. The earliest thalamic neurons, originating from the ventricular neuroepithelium between embryonic days 13 and 15, include those of the reticular thalamic nucleus. At this developmental stage, calretinin, calbindin or gamma-aminobutyric acid immunostaining revealed both radially and nonradially orientated neurons in the region of reticular thalamic migration, between the dorsal and ventral thalamic primordia. In cultured slices, injections of fluorescent dyes in the neuroepithelium labelled neurons in a migratory stream along radial glia in the same zone. Some labelled fusiform cells departed from this radial trajectory along orthogonal routes within the dorsal thalamus. Confocal microscopy revealed nonradially orientated neurons in close apposition with a fibre system parallel to the lateral thalamic surface. These fibres expressed axonal markers, including the intermediate filament protein alpha-internexin and a polysialylated form of neuronal cell adhesion molecule. Active migration of nonradially orientated neurons along neuronal substrates was confirmed in living cultured slices. In addition, in vitro and ex vivo experiments revealed neurons migrating tangentially in association with glial fibres. These results provide novel evidence that: (i) early generated thalamic neurons follow nonradial routes in addition to glia-linked radial migration; and (ii), nonradially migrating thalamic neurons move along both glial and axonal substrates, which could represent a distinctive feature of thalamic development.

Localization of ApoER2, VLDLR and Dab1 in radial glia: groundwork for a new model of reelin action during cortical development.

The reelin signaling pathway regulates laminar positioning of radially migrating neurons during cortical development. It has been suggested that reelin secreted by Cajal-Retzius cells in the marginal zone could provide either a stop or an attractant signal for migratory neurons expressing reelin receptors, but the proposed models fail to explain recent experimental findings. Here we provide evidence that the reelin receptor machinery, including the lipoprotein receptors ApoER2 and VLDLR along with the cytoplasmic adaptor protein Dab1, is located in radial glia precursors whose processes span the entire cortical wall from the ventricular zone to the pial surface. Moreover, in reeler mice, defective in reelin, decreased levels of Dab1 in the ventricular zone correspond to an accumulation of the protein in radial end-feet beneath the pia matter. Our results support that neural stem cells receive a functional reelin signal. They are also consistent with a working model of reelin action, according to which reelin signaling on the newborn neuron-inherited radial process regulates perikaryal translocation and positioning.

The surface of the developing cerebral cortex: still special cells one century later.

The marginal zone of the developing cerebral cortex is formed by different types of neurons, some of which were described more than one century ago. It is the case of Cajal-Retzius cells, which are known to synthesize and secrete Reelin, an extracellular matrix glycoprotein critically involved in the radial migration and early cortical cytoarchitectonic organization. These cells do not emit projection axons, a characteristic that bespeaks against these cells being considered as pioneer neurons. The true pioneer neurons of the marginal zone are part of a distinct cell entity: these are cells that emit the earliest descending axonal projection from the cerebral cortex into the subpallium, even before than subplate neurons, the other population of pioneer neurons in the cortical anlage. Finally, the marginal zone is a territory where cohorts of undifferentiated cortical interneurons migrate into the upper layers of the cerebral cortex. Marginal zone neurons, including Cajal-Retzius cells, tend to distribute non-uniformly over the cortical surface. Such a mosaic structural configuration points towards more complexities regarding their possible functions during cortical development.

Making scents of olfactory neurogenesis.

Olfaction was long considered to belong more to the realm of art than to that of science. As a result, how the brain perceives, discriminates, and recognizes odorant molecules is still a mystery. Recent progress has nonetheless been made at early stages of the olfactory pathway when olfactory studies entered into the molecular era to elucidate the first contact of an odor molecule with a receptor. Our group focuses on the analysis of odor information in the olfactory bulb, the first processing relay in the mammalian brain. Using this model, we are attempting to decipher the code for odorant information. Furthermore, the olfactory bulb also provides an attractive model to investigate neuronal proliferation, differentiation, migration, and neuronal death, processes involving an interplay between genetic and epigenetic influences. Finally, our goal is to explore the possible consequences of the olfactory bulb plasticity, in olfactory performance. For these purposes, we aim to combine morphological, electrophysiological and behavioral approaches to investigate: (1) how the olfactory bulb processes odor molecule information, (2) how neural precursors differentiate into olfactory bulb interneurons, (3) how these newly-generated neurons integrate into an operational neural network, (4) what role they play in the adult olfactory bulb, and (5) how are basic olfactory functions maintained in such a sensory system subjected to continuous renewal of a large percentage of its neuronal population. These questions should provide new fuel for the molecular and cellular bases of sensory perception and shed light onto cellular bases of learning and memory.