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.