Elizabeth Grove

Professor

Department of Neurobiology

The University of Chicago
947 E. 58th St., MC0926
Chicago, IL 60637

Email: grove@bsd.uchicago.edu
Phone: (773) 702-9909
Office: Abbott 220

 

Research Summary

Cellular and molecular mechanisms that drive development of cerebral cortex

 

Research Statement

How does a simple sheet of dividing cells develop into the complex mammalian cerebral cortex, controlling higher brain functions such as perception, cognition and memory?  We address this question for two different types of cortex, neocortex and the hippocampus. 

Neocortex is divided into a map of functionally specialized areas, an organization that seems fundamental to how neocortex works. Across many mammalian species the relative positions of primary sensory and motor areas in the map are similar, suggesting that mechanisms generating basic features of the map are conserved. Using gene expression assays, mouse genetics and a novel method of gene transfer in mouse embryos in utero, we identified two embryonic signaling centers for the cortical primordium –conserved in mouse, ferret and chick.  One, termed the “cortical hem”, produces powerful developmental signaling proteins of the WNT (Wingless/Int) and BMP (Bone Morphogenetic Protein) families, and is both necessary and sufficient for the formation of a hippocampus. Following on from these findings, we now want to discover the mechanisms that divide the hippocampus into distinct fields and direct their typical connections and functions. 

The second signaling center is near the rostral cortical primordium and generates FGF proteins (Fibroblast Growth Factors), FGF8 and 17.  These molecules disperse in gradients from the source, providing positional values to the cortical primordium and initiating map formation.  Thus, if a new source of FGF8 is experimentally introduced into a mouse embryo near the original source, excess FGF8 pushes cortical area boundaries caudally.  If the new source is at the opposite, caudal pole of the primordium, the dual (and dueling) signal sources create duplicate areas.  We are now searching for genes downstream of FGF8 that regulate the features that characterize mature areas.  A further goal is to determine how patterning mechanisms intrinsic to the neocortical primordium interact with emerging brain activity.

 

Select Publications

Caronia-Brown G, Yoshida M, Gulden F, Assimacopoulos S, Grove EA. (2014) The cortical hem regulates the size and patterning of neocortex. Development. 2014 Jul;141(14):2855-65.

Assimacopoulos S., Kao T., Issa N.P., Grove E.A. (2012) Fibroblast Growth Factor 8 Organizes the Neocortical Area Map and Regulates Sensory Map Topography. J. Neurosci. 32:7191–7201.

Pani A.M., Mullarkey E.E., Aronowicz J., Assimacopoulos S., Grove E.A. Lowe C.J. (2012) Ancient deuterostome origins of vertebrate brain signaling centres. Nature 483:289-94.

Toyoda RAssimacopoulos SWilcoxon JTaylor AFeldman PSuzuki-Hirano AShimogori TGrove E.A. (2010)  FGF8 acts as a classic diffusible morphogen to pattern the neocortex. Development 137:3439-48.

Grove, E.A. (2008) Organizing the source of memory, Perspective in Science. 319: 288-9.

Yoshida, M., Assimacopoulos, S., Jones K.R., and Grove, E.A., (2006) Massive Loss of Cajal Retzius Cells Does Not Disrupt Neocortical Layer Order.  Development. 133: 537-545.

Shimogori, T. and Grove, E,A. (2005) FGF8 regulates intracortical guidance of area-specific thalamic innervation. J. Neurosci.25:6550–6560.

Abu-Khalil A., Fu, L., Grove, E,A., Zecevic, N., Geschwind, D.H. (2004) Wnt genes define distinct boundaries in the developing human brain: Implications for human forebrain patterning. J. Comp. Neurol. 474: 276-288.

Fukuchi-Shimogori, T. and Grove, E,A. (2001) Patterning of the neocortex by the secreted signaling molecule FGF8. Science. 294: 1071-1074.

Tole, S. and Grove, E.A. (2001) Detailed field pattern is intrinsic to the embryonic mouse hippocampus early in neurogenesis.  J. Neurosci.  21: 1580–1589.

Lee, S.M., Tole, S., Grove, E,A. and McMahon, A.P. (2000). A local Wnt3a signal is required for development of the mammalian hippocampus. Development 127: 457-467.

Full bibliography available at: http://www.ncbi.nlm.nih.gov/sites/myncbi/1VSM_Rk0a7oA_/bibliography/47404694/public/?sort=date&direction=descending