Research Summary

We explore the mechanisms that regulate pattern formation and growth in the vertebrate forebrain. Several projects 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. Our goal is to discover how the cortical area map is generated. We are testing a model in which signaling molecules released from discrete sources in and near the embryonic cortex provide early positional information and exert regional growth control. To test this model we are 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, their receptors and regulators. We use both conditional and standard gene targeting and a novel method of gene transfer in living mouse embryos (in utero electroporation) to identify molecular mechanisms that generate the area map. Projects also include genetic fate mapping to determine the sources of particular cortical cell types, and studies of the mechanisms of complex neuronal migrations.

Selected Papers

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. (online)

Grove, E,A. and Fukuchi-Shimogori, T. (2003) Generating the cerebral cortical area map. Ann. Rev. Neurosci. 2003. 26:355-80.

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

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.

Belmadani, A., Tran, P. B., Ren, D. Assimacopoulos, S., Grove, E.A., Miller, R. (2005) The chemokine SDF-1 regulates the migration of sensory neuron progenitors. J. Neurosci. 25:3995-4003.

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

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. (online)

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