Seth Grant - Bio-sketch

Differential gene expression underlies differential cellular phenotype in the nervous system, and individual gene expression patterns have long been used to delineate functionally discrete neuroanatomical subdivisions.  This type of approach to define the genetic architecture, or “molecular anatomy,” of the brain has been radically bolstered by the recent availability of genome-scale cellular resolution in situ hybridization data in the Allen Brain Atlas and related databases.  In particular, the mapping of these data to standardized anatomical models allows statistical analyses across these large data sets to understand genetic regional parcellation and interrelationships.  In the current study, a variety of statistical clustering methods and classical anatomical techniques were used to examine the genetic architecture of the adult mouse hippocampus across the entire Allen Brain Atlas data set.  These data demonstrate a robust genetic correlate to the classical anatomical parcellation of the hippocampus into dentate gyrus, CA1, CA2 and CA3 fields, but also an unanticipated degree of molecular heterogeneity along the septotemporal axis of the hippocampus as well.  While individual gene expression patterns are highly diverse, as a set these data show a coherent, complex cellular organization represented by unique combinatorial gene expression patterns highly representing functionally relevant gene families such as transcription factors, ion channels and cell adhesion molecules.  This approach to “genomic neuroanatomy” provides both high level organizational principles and a high resolution map of gene expression profiles to guide functional studies, and should be a powerful strategy to expand upon as more large-scale gene expression data sets become available.