Title

Genetic mechanisms that determine the identity and function of thalamic and habenular cells in the mouse diencephalon

Date of Completion

January 2012

Keywords

Biology, Genetics|Health Sciences, Human Development

Degree

Ph.D.

Abstract

The developing vertebrate forebrain consists of the major divisions of telencephalon and diencephalon. The diencephalon gives rise to the hypothalamus, prethalamus, thalamus, habenula and pretectum. While the telencephalon has been majorly researched upon, a lot remains unknown about diencephalic development, more precisely the origin and the genetic mechanisms that generate the diverse connectivity patterns that are seen in the neurons of the various sub-divisions of the diencephalon. The goal of this project was to study the genetic mechanisms that are involved in the development of mouse diencephalic neurons from their progenitor stage towards maturity. Pax6 is a paired domain containing transcription factor expressed broadly in the progenitors and some of the post-mitotic cells of the diencephalon. I have identified Pax6 as a key regulator for restricting the domain specific expression of proneural genes and also post-mitotic gene expression in both the habenula and thalamic subdivisions of the diencephalon. These functions of Pax6 are mediated at least in part by SIM. Gbx2 is a homeodomain containing transcription factor that is exclusively expressed in post-mitotic cells of the thalamus. In a separate study, I have found that loss of Gbx2 function leads to ectopic expression of habenular and pretectal markers in the thalamic cells. Gbx2 thereby functions in determining the identity of these cells. Lastly, I have also identified that along with LIM-HD transcription factors Lhx2 and Lhx9 as partners, Gbx2 determines thalamic neuron connectivity by cell-autonomously regulating the dynamic expression pattern of axon guidance receptors Robol and Robo2 in the thalamic cells. ^