Person:

Maroof, Asif

Summary Evolutionary elaboration of tissues starts with changes in the genome and location of the stem cells. For example, GABAergic interneurons of the mammalian neocortex are generated in the ventral telencephalon and migrate tangentially to the neocortex, in contrast to the projection neurons originating in the ventricular/subventricular zone (VZ/SVZ) of the dorsal telencephalon. In human and nonhuman primates, evidence suggests that an additional subset of neocortical GABAergic interneurons is generated in the cortical VZ and a proliferative niche, the outer SVZ. The origin, magnitude, and significance of this species-specific difference are not known. We use a battery of assays applicable to the human, monkey, and mouse organotypic cultures and supravital tissue to identify neuronal progenitors in the cortical VZ/SVZ niche that produce a subset of GABAergic interneurons. Our findings suggest that these progenitors constitute an evolutionary novelty contributing to the elaboration of higher cognitive functions in primates.

Using transgenic animals harboring a targeted LacZ insertion, we studied the expression pattern of the C9ORF72 mouse ortholog. Unlike most genes mutated in ALS, which are ubiquitously expressed, the C9ORF72-ortholog was most highly transcribed in the neuronal populations sensitive to degeneration in ALS and FTD. Thus, our study provides a potential explanation for the cell type specificity of neuronal degeneration caused by C9ORF72 mutations.