The neuronal membrane glycoprotein M6a (Gpm6a) functions in the processes of neuronal differentiation and development and its function in the differentiation of neurons derived from mouse and human embryonic stem cells has been shown recently. Diverse neuropsychiatric diseases such as depression, schizophrenia, claustrophobia, Alzheimer’s disease, and learning disability have been linked to the alteration in GPM6A expression levels or sequence.
In the present project we propose to employ technology human induced pluripotent stem cells (iPSCs) as an alternative approach to study the role of Gpm6a in neuropsychiatric disease in the human context. The central hypothesis to be tested is that the Gpm6a functions in differentiation of medial ganglionic eminence (MGE) progenitors and neurons derived from human iPSCs. MGE progenitors serve as precursors to GABA interneurons and basal forebrain cholinergic neurons (BFCNs), two cell types that are relevant in numerous neuropsychiatric diseases such as schizophrenia, autism, intellectual disabilities, and Alzheimer’s disease, among others.
Our aim is to use iPSCs differentiated into MGE progenitors to study functional consequences of the presence or absence of Gpm6a in the development of human brain tissues. Here iPSC lines will be generated and differentiated toward MGE progenitors and endogenous Gpm6a expression will be evaluated by qPCR and immunocytochemistry throughout the course of neural differentiation of iPSCs.