Department of Neurobiology
The University of Chicago
947 E. 58th St., MC0926
Chicago, IL 60637
Phone: (773) 702-9909
Office: Abbott 220
Cellular and molecular mechanisms that drive early brain development
We explore the mechanisms that regulate pattern formation in the vertebrate forebrain. We focus on the development of the mammalian cerebral cortex, the part of the brain that controls higher functions. Neocortex is divided into many functionally specialized areas, forming an area map that is fundamental to the way neocortex works in the adult animal. The position and size of areas in the area map are similar from one individual to another in a given species, and there are common features across mammalian species. We are testing a model of how the area map is generated in which signaling centers in and near the embryonic cortex provide early positional information and initiate the area map. To test this model we examine the function 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, called in utero microelectroporation, to identify molecular mechanisms that generate the cortical area map. We have found that FGF8, which is produced at the anterior end of the embryonic cortex is a key player in initiating cortical area pattern. Introducing new sources of FGF8 into the embryonic cortex creates duplicate areas and even duplicate area maps. Our findings raise questions about the genes that act downstream of FGF8 to generate the features, including connectivity and physiological function, that characterize different areas. A second area of interest is how the hippocampus, required for memory, is induced to form in the embryonic brain. Projects include 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.
Tole, S., Ragsdale, C.W. and Grove, E,A. (2000). Dorsoventral patterning of the telencephalon is disrupted in the mouse mutant extra-toesJ. Dev. Biology 217: 254-265.
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.
Fukuchi-Shimogori, T. and Grove, E,A. (2001) Patterning of the neocortex by the secreted signaling molecule FGF8. Science. 294: 1071-1074.
Fukuchi-Shimogori, T. and Grove, E,A. (2003) Emx2 patterns the neocortex by regulating FGF positional signaling. Nature Neurosci. 6:825-31.
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.
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.
Shimogori, T. and Grove, E,A. (2005) FGF8 regulates intracortical guidance of area-specific thalamic innervation. J. Neurosci.25:6550–6560.
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.
Rash, B. G. and Grove E. A. (2007) Patterning the dorsal telencephalon: a role for Sonic hedgehog? J Neurosci. 27:11595-603.
Grove, E.A. (2008) Organizing the source of memory, Perspective in Science. 319: 288-9.