Neurovascular congruence during cerebral cortical development.

There is evidence for interaction between the developing circulatory and nervous systems. Blood vessels provide a supporting niche in regions of adult neurogenesis. Here we present a systematic analysis of vascular development in the embryonic murine cortex and demonstrate that dividing cells, including Tbr2-positive intermediate progenitor cells, are closer to the vasculature than expected from a random distribution.

ERK5 MAP kinase regulates neurogenin1 during cortical neurogenesis.

The commitment of multi-potent cortical progenitors to a neuronal fate depends on the transient induction of the basic-helix-loop-helix (bHLH) family of transcription factors including Neurogenin 1 (Neurog1). Previous studies have focused on mechanisms that control the expression of these proteins while little is known about whether their pro-neural activities can be regulated by kinase signaling pathways. Using primary cultures and ex vivo slice cultures, here we report that both the transcriptional and pro-neural activities of Neurog1 are regulated by extracellular signal-regulated kinase (ERK) 5 signaling in cortical progenitors.

Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex.

The developing cerebral cortex contains apical and basal types of neurogenic progenitor cells. Here, we investigated the cellular properties and neurogenic output of basal progenitors, also called intermediate neuronal progenitors (INPs). We found that basal mitoses expressing transcription factor Tbr2 (an INP marker) were present throughout corticogenesis, from embryonic day 10.

Role of intermediate progenitor cells in cerebral cortex development.

Intermediate progenitor cells (IPCs) are a type of neurogenic transient amplifying cells in the developing cerebral cortex. IPCs divide symmetrically at basal (abventricular) positions in the neuroepithelium to produce pairs of new neurons or, in amplifying divisions, pairs of new IPCs. In contrast, radial unit progenitors (neuroepithelial cells and radial glia) divide at the apical (ventricular) surface and produce only single neurons or single IPCs by asymmetric division, or self-amplify by symmetric division.

Organotypic slice culture of embryonic brain tissue.

INTRODUCTIONThis protocol describes how to dissect, assemble, and cultivate mouse embryonic (E) brain tissue from age E11.5 to E18.5 (days) for organotypic slice culture.

Unipolar brush cells of the cerebellum are produced in the rhombic lip and migrate through developing white matter.

Unipolar brush cells (UBCs) are glutamatergic interneurons in the cerebellar cortex and dorsal cochlear nucleus. We studied the development of UBCs, using transcription factor Tbr2/Eomes as a marker for UBCs and their progenitors in embryonic and postnatal mouse cerebellum. Tbr2+ UBCs appeared to migrate out of the upper rhombic lip via two cellular streams: a dorsal pathway into developing cerebellar white matter, where the migrating cells dispersed widely before entering the internal granular layer, and a rostral pathway along the cerebellar ventricular zone toward the brainstem.

Transcription factors in glutamatergic neurogenesis: conserved programs in neocortex, cerebellum, and adult hippocampus.

Glutamatergic, pyramidal-projection neurons are produced in the embryonic cerebral cortex by a series of genetically programmed fate choices, implemented in large part by developmental transcription factors. Our work has focused on Pax6, Tbr2/Eomes, NeuroD, and Tbr1, which are expressed sequentially during the neurogenesis of pyramidal-projection neurons. Recently, we have found that the same transcription factors are expressed, in the same order, during glutamatergic neurogenesis in the adult dentate gyrus, and (with modifications) in the developing cerebellum.

Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip.

The deep cerebellar nuclei (DCN) are the main output centers of the cerebellum, but little is known about their development. Using transcription factors as cell type-specific markers, we found that DCN neurons in mice are produced in the rhombic lip and migrate rostrally in a subpial stream to the nuclear transitory zone (NTZ). The rhombic lip-derived cells express transcription factors Pax6, Tbr2, and Tbr1 sequentially as they enter the NTZ.

Aberrant neuronal-glial differentiation in Taylor-type focal cortical dysplasia (type IIA/B).

Focal cortical dysplasia (FCD) type IIA/B (Taylor type) is a malformation of cortical development characterized by laminar disorganization and dysplastic neurons. FCD IIA and FCD IIB denote subtypes in which balloon cells are absent or present, respectively. The etiology of FCD IIA/B is unknown, but previous studies suggest that its pathogenesis may involve aberrant, mixed neuronal-glial differentiation.

Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex.

The developing neocortex contains two types of progenitor cells for glutamatergic, pyramidal-projection neurons. The first type, radial glia, produce neurons and glia, divide at the ventricular surface, and express Pax6, a homeodomain transcription factor. The second type, intermediate progenitor cells, are derived from radial glia, produce only neurons, and divide away from the ventricular surface.

March 2004: a 24-year-old woman with bifrontal headaches.

A 24-year-old woman with bifrontal headaches was found to have a well-circumscribed lesion in the frontal lobe subcortical white matter. Microscopic examination showed clusters of small round cells separated by hypocellular neuropil-like areas, and a distinct border between tumor and surrounding white matter. Synaptophysin was diffusely positive in neuropil-like areas, and many tumor cells expressed NeuN.

Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons.

Cortical projection neurons exhibit diverse morphological, physiological, and molecular phenotypes, but it is unknown how many distinct types exist. Many projection cell phenotypes are associated with laminar fate (radial position), but each layer may also contain multiple types of projection cells. We have investigated two hypotheses: (1) that different projection cell types exhibit characteristic molecular expression profiles and (2) that laminar fates are determined primarily by molecular phenotype.

Cajal-Retzius cells in the mouse: transcription factors, neurotransmitters, and birthdays suggest a pallial origin.

Cajal-Retzius cells are reelin-secreting neurons found in the marginal zone of the mammalian cortex during development. Recently, it has been proposed that Cajal-Retzius cells may be generated both early and late in corticogenesis, and may migrate into the cortex from proliferative zones in the subpallium (lateral ganglionic eminence and medial ganglionic eminence) or cortical hem. In the present study, we used reelin as a marker to study the properties of Cajal-Retzius cells, including their likely origins, neurotransmitters, and birthdates.