PhD Research Scholar Manipal Academy of Higher Education Manipal, Karnataka, India
Abstract: In the intricate landscape of brain development, clusters of interneurons, originating from specific progenitor domains, undergo long-distance migration within the developing telencephalon to establish neural connections and form the central inhibitory system of the brain. A disturbance in this balance, often resulting from anomalies in migration, has been implicated as the pathogenesis of several neurodevelopmental disorders. This underscores the critical significance of neuronal migration in shaping the cellular functions and neuronal circuitry of the neocortex. Here, we aimed to elucidate the role of molecular regulators guiding the interneuron migration through human pluripotent stem cell-derived medial ganglionic eminence cells through a 25-day directed differentiation protocol. A detailed radial migration assay was performed to identify the temporal migration of interneuron progenitors. Subsequently, mRNA and miRNA sequencing at two critical time points identified from the migration assay was performed to decipher the genes involved in human interneuron migration. The results of next-generation sequencing of enriched microRNAs from two distinct groups- one displaying minimal migration potential and another with maximum migration potential unveiled a total of 419 known and novel miRNAs, of which 138 miRNAs were differentially expressed between groups. In addition, 31 mature microRNAs were expressed exclusively on attaining maximum migratory potential. Further extensive analysis identified that several of these microRNAs control mRNAs that are involved in interneuron migration. Thus, the identified microRNAs contribute to the evolving understanding of the regulatory role of miRNAs in inhibitory GABAergic interneuron development. Furthermore, it explores the implications of their dysregulation in the emergence of numerous neurodevelopmental and neuropsychiatric disorders.
Funding Source: Science and Engineering Research Board, Government of India
