Transcriptomic contributions to the development and evolution of the human cerebral cortex - Project Summary The development of the human brain is a highly coordinated process involving the controlled expression of thousands of genes, where deviations from this genetic code can result in neurological conditions or deficits in cognition and behavior. Thus, it is crucial to understand the complexities of gene expression variation of the cortical transcriptome in the human brain across all life-stages. Recently, with advancements in sequencing technology, researchers can now examine the transcriptomic heterogeneity in humans and correlate these variations to neuroanatomical and functional properties of the brain. Prior research in adults has shown that a small subset of genes is indeed related to regional variability in function and neuroanatomy, but it is still presently unknown how this translates across development. Thus, this project aims to identify which genes are highly variable across all developmental stages, what neuroanatomical properties these genes are associated with, their localized and cell type expression, and which are specific to human development. Findings from this project will complement those from early prenatal stages, which has been heavily researched, and will provide novel insights for later stages of development, primarily across childhood and adolescence. To carry out the proposed research, the applicant will implement a novel pipeline established in the lab that identifies genes most differentially expressed across development in both humans and macaques, carry out gene enrichment and network analyses, spatially localize identified gene expression patterns, and determine related neuroanatomical properties through cross-modal neuroimaging analyses. Both aims will take advantage of publicly available transcriptomic atlases. Aim 1 will examine the transcriptomic variability across human development using bulk RNA sequencing analyses and in situ hybridization. Aim 2 will then apply the same methods from Aim 1 on transcriptomic data from macaques in order to make cross- species comparisons and to identify which genes from Aim 1 are human-specific. Findings from these approaches will identify novel sets of human-related genes that are crucial to various stages of development and ultimately, will be beneficial to applications in mental health. The two sponsors of this project, Profs. Kevin Weiner and Silvia Bunge, along with thesis committee member Dr. Mercedes Paredes, will provide relevant expertise and guidance in the field of neuroanatomy, development, and transcriptomics. Additionally, support from consultants and resources from UC Berkeley and the Helen Wills Neuroscience institute will ensure that the applicant successfully completes the dissertation and is prepared for a competitive post-doctoral fellowship and research career investigating the transcriptomic basis of human brain development.
