A regulatory element for interneuron progenitors in the developing vertebrate central nervous system

Evangeline Tzatzalos
2012
The development of the central nervous system (CNS) is regulated by non-protein coding gene regulatory elements that control the expression of neural stem cell genes via the interaction of protein trans-acting factors. As a result of recent progress in neuroscience and biotechnology, valuable insight into neural cell growth has been attained from important components of the neural stem cell protein expression profile. However, the role of cis-regulatory elements (non-protein coding genomic DNA
more » ... coding genomic DNA on the same molecule) in neural stem cells remains confounded. A cis-regulatory element of neural progenitors during vertebrate development has been identified and characterized. This regulatory element is a conserved, non-protein coding region located within the established neural stem cell gene, Notch1. Notch1 is expressed in radial glia, which are self-renewing, neural stem/progenitor cells with long processes that serve as scaffolds for neuronal migration. A conserved non-coding region in the Notch1 locus (i.e., Notch1CR2) is active exclusively in the ventral CNS during neurogenic periods. On a cellular level, it is active in asymmetrically dividing cells that give rise to GABAergic interneuron progenitors and interneurons. Notch1CR2 is a novel regulatory element for interneuron progenitors. In this thesis, four studies of Notch1CR2 are presented. In the first study, CNS-specific regulatory activity of Notch1CR2 is revealed during chick embryonic development using in ovo electroporation. Second, the temporal-spatial profile of Notch1CR2 activity is determined to be present in cells with an interneuron progenitor phenotype using a transgenic mouse model. Third, the molecular mechanism of Notch1CR2 is investigated, and potential binding trans-acting factors of Notch1CR2 are identified. Finally, Notch1CR2 reveals a change in the interneuron progenitor population in the reeler mutant mouse compared to the wildtype. Reeler is a mutant mouse with deficiencies in neuronal migration and lamination. The discovery [...]
doi:10.7282/t3gq6wq4 fatcat:53gimfk4tjcvvgwljr7gxsehwy