Resumen de Development of neuronal lineages in the mammalian cerebral cortex
Neuronal circuits in the cerebral cortex arise through the assembly of two main neuronal elements: inhibitory GABAergic interneurons and excitatory glutamatergic pyramidal cells. Each group of neurons is highly diverse and play a different role during cortical function. Pyramidal cells are primarily involved in transmitting long-range information while interneurons mostly shape the activity of pyramidal cells via local inhibition.
Pyramidal cells and interneurons are generated in distinct and distant proliferative regions in the embryonic brain and adopt different strategies to reach the cortex and organize through layers and columns, the main histological and functional hallmarks of cortical cytoarchitecture. Thus, functional circuits arise from early developmental processes, such as neurogenesis and cell migration that guide the precise assembly of cortical neurons.
In this Thesis, we have investigated the contribution of progenitor cells to the generation of cell diversity and how lineage relationships influence the organization of cortical neurons by developing a new method to tag individual progenitors and trace their progenies with regional/subtype specificity in vivo. Analyses of cell distributions revealed that all three major classes of interneurons have a strong tendency to organize in discrete cellular clusters in the adult cortex. Individual clusters are composed by either the same or different interneurons subtypes and largely consist of isochronic interneurons that primarily arrange along the laminar dimension of the neocortex. Moreover, our results point out to the existence of interneuron progenitor cell classes that are fate-restricted to generate interneurons for specific cortical layers, in a model that links progenitor cell heterogeneity with the laminar restriction of interneuron lineages.
Similar fate-mapping analyses of pyramidal cells progenitors suggest that multipotent and fate-restricted progenitor cells coexist during cortical development, perhaps with a different contribution of progenitors types respect to interneuron lineages. All together our findings open new perspectives for our understanding of the development of inhibitory and excitatory neurons and their assembly into nascent cortical circuits.
