Elizabeth A. Grove


Elizabeth A. Grove (left) and Tomomi Fukuchi-Shimogori (right)

Professor

Address: Abbott 220
Phone: 773-702-9909
Email: egrove@bsd.uchicago.edu

Primary:

Department of Neurobiology

Secondary:

Committee on Neurobiology
Committee on Developmental Biology
Committee on Cancer Biology

Research Synopsis

Development of the mammalian neocortex and hippocampus

Research Description
    We explore the mechanisms that regulate pattern formation and growth in the vertebrate forebrain. We focus on the development of the mammalian cerebral cortex, the part of the brain that controls higher functions.  Cerebral cortex is divided into many functional areas, and this organization is fundamental to how the cortex works in the mature animal.
    We are testing a new model of how the cortical area map is generated.  In this model signaling molecules released from discrete centers in and near the embryonic cortex provide early positional information and exert regional growth control.  These signals set up developmental domains in the cortex that are characterized by the expression of specific transcription factors.  By regulating expression of other genes, these transcription factors control further area specification and growth.  To test this model we are investigating newly identified signaling centers and examining the roles in mouse cortical development of the Wnt (Wingless/Int), Bmp (Bone Morphogenetic Protein) and FGF (Fibroblast Growth Factor) families of signaling proteins.  We use both gene targeting and a novel method of gene transfer in living mouse embryos to identify molecular mechanisms that generate the cortical area map.  Projects also involve directed searches for novel genes involved in neocortical and hippocampal development.  Comparative studies of cortical development are planned to gain insight into how cortex is assembled in different species, and how cortical organization may have evolved.

Selected References
Grove, E. A., Tole, S., Limon, J., Yip, L.-w. and Ragsdale, C. W. (1998)
The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice. Development 125: 2315-2325.

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. Development127: 457-467.

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

Lu, M., Grove, E.A. and Miller, R.J. (2002)
Abnormal development of the hippocampal   dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A. 99:7090-5.

Grove, E.A. and Fukuchi-Shimogori, T.  (2003)
Generating the Cerebral Cortical Area Map.  Ann. Rev. Neurosci. 26:355-80

Fukuchi-Shimogori, T. and Grove, E.A. (2003)
Emx2 patterns the neocortex by regulating FGF positional signaling. Nature Neurosci.6:825-31.

Shimogori, T., Banuchi, V., Ng, H.Y., Strauss, J. and Grove, E.A.  (2004)
Embryonic signaling centers expressing BMP, Wnt and FGF proteins interact to pattern the cerebral cortex. Development 131:5639-5647.

Louvi, A., Sisodia, S.S. and Grove, E.A.  (2004)
Presenilin1 in morphogenesis and migration in the central nervous system.  Development 131:3093-3105

Shimogori, T., and Grove, E.A.  (2005)
Fibroblast growth factor 8 regulates neocortical guidance of area-specific thalamic innervation.  J Neurosci. 25:6550-60.
 
Updated 8/3/06