The role of type III neuregulin1 in birth and migration of neurons in the embryonic and adult forebrain.

摘要

Neuregulin1 isoforms play roles in both embryonic and adult neuronal proliferation, radial and tangential migration of neurons in the developing and adult CNS, as well as in maturation and maintenance of synapses. I used the reduction of Type III Nrg1 protein in developing and adult Type III Nrg1 heterozygous mutant mice as a means of assessing the normal roles of Type III Nrg1 in the CNS. My results show that specific subtypes of interneurons in select brain regions and nuclei are affected by reduced Type III Nrg1, while other subtypes are unaffected. I show that reduced Type III Nrg1 results in decreased number of GABAergic interneurons in the prelimbic and infralimbic cortex, cholinergic interneurons in the striatum, and a decreased number of dopaminergic interneurons in the olfactory bulb that can in part be accounted for by a decrease in adult neurogenesis. I propose a cohesive mechanism whereby reduced Type III Nrg1 can have apparently disparate effects. These results have the potential to inform translational research into the ways in which alterations in genotype can manifest as a complex neurological and/or psychiatric phenotype.