Understanding and Characterizing the Interaction Between LHX2 and KDM1A (LSD1) and its Role in Neocortical Development

Sengupta, Rohin (2023) Understanding and Characterizing the Interaction Between LHX2 and KDM1A (LSD1) and its Role in Neocortical Development. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Rohin Sengupta (18MS126)) Thesis_18MS126.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

The neocortex has a key role to play in higher cognitive processes. Disorders that arise from improper development of the neocortex have the potential to result in significant intellectual and social disabilities. Understanding the diseases and underlying mechanisms of the neocortex's development serve a dual purpose in facilitating the development of therapeutic strategies to deal with these disorders, and also help elucidate the role that the neocortex plays in our functioning. Six unique anatomical layers, with alternate cell densities, define the neocortex. Prior to the onset of neurogenesis, neuroepithelial stem cells (NESCs) form the neuroepithelium. The cortical neurogenesis begins with NECs shifting to asymmetric cell division, generating downstream cell types such as apical intermediate progenitors, basal progenitors, or postmitotic neurons. The nucleosome remodelling and deacetylase (NuRD) complex, which plays a crucial role in regulating chromatin in neural stem cells, is a vital factor in the development of functional neural networks. The NuRD complex combines chromatin remodelling and protein deacetylase activities and consists of two subcomplexes: the remodelling and deacetylase subcomplex. The complex is involved in proliferation, differentiation, migration, and complex network formation, which are the foundation for higher-order cognitive and behavioural functions. Another protein of interest in the context of neocortical development is LHX2. LHX2 regulates the differentiation of radial glial cells, and its deletion leads to severe neocortical malformations. Additionally, LHX2 regulates the expression of several key developmental genes, and its deficiency may lead to aberrant neurogenesis, thereby underlining its critical role in neocortical development. Understanding the intricate and dynamic regulation of chromatin, by chromatin remodellers, and the role of specific transcription factors such as LHX2 could potentially contribute to the development of novel therapies for neocortical developmental disorders.

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