Gene co-expression tools applied to the developing thalamus
Oliver Duocastella, Xavier
Duocastella, Xavier Oliver
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This project contributes to the understanding of how the thalamus, a major structure in the mammalian brain, develops. This is done through the creation and application of neuroinformatics tools to biological data. The thalamus is a paired structure located ventro-caudally in the vertebrate forebrain which constitutes the most important part of the diencephalon. Its main roles are the relay of sensory information from the body to the brain, and the modulation of this information based on feedback it receives. Internally it is subdivided into nuclei, big cell clusters that belong to separate pathways. The parcellation of the thalamus into nuclei starts embryonically, where multiple genes with combinatorially overlapping expression patterns help differentiate the fate of newly formed cells. Based on nuclei counterstain and gene expression in situ data from the Allen Developmental Mouse Brain Atlas, this project provides insights on how the mouse thalamus is parcellated at E13.5. To do so, methods are proposed to extract cell density information from reference datasets and single gene expression information. A workflow is described to unify the data from the two methods into the same anatomical space. A method to calculate levels of co-expression between pairs of genes is then developed, providing a way to categorise pairs of genes based on their co-expression relationship in a specific brain region: no co-expression, potential, or existent. The tools implementing the methods are then applied to the combinations of several genes involved in different developmental aspects of the thalamus at E13.5 (Gbx2, Ngn2, Olig2, Otx2, Cdh8 and EphA4), to understand where cells co-express or might coexpress each pair. The results indicate that the more restricted nature of co-expression patterns of gene pairs is more useful to understand nucleogenesis than individual gene expression patterns, which might be too wide or too specific. Finally a subdivision of the developmental thalamus at this age is proposed based on the regions in common, and these subdivisions are linked to the adult thalamus.