RAGSDALE LAB WEB PAGE

I am interested in how the neurons and circuitry of the vertebrate central nervous system are specified during development. In vertebrate brains, neurons with similar long-distance connections are aggregated into neural centers known as nuclei. Dozens of nuclei can be distinguished in the brains of birds and mammals, and connections among neurons in these brains are in essence connections targeted to different nuclei. Viewed from this perspective, the problem of how neurons make the correct connections with one another in early development is, for studies of vertebrates, a problem of pattern formation: how are neurons allocated to different nuclear fates? and how are nuclei formed? 

My laboratory employs cellular and molecular techniques to ask how the neurectoderm is organized at the time of nucleogenesis and to investigate the developmental mechanisms responsible for pattern generation and neuron cell-type specification.  We identify emerging nuclear patterns by the early organization of axonal connections and by the expression of marker genes, including signaling molecules and position-dependent transcription factors, isolated by motif-based cloning strategies and genome database searches.  cDNAs for these marker genes are, in turn, candidates for misexpression experiments to probe the genetic mechanisms that mediate the acquisition of neuronal identity in brain nuclei. 

Our research is carried out in chicks and mice.  The chick brain is accessible throughout development for fate mapping and cell lineage studies, experimental embryology including tissue transplants, and genetic manipulation by recombinant retrovirus infection and in ovo electroporation.  Research on the mouse embryo offers a broad range of reverse genetic technologies and a number of established mutants.  The major effort of our current work is on two projects, how the nuclei of the midbrain are patterned in early development and how the parcellation of the cerebral cortex into functionally distinct areas takes place. 
 

References

Agarwala, S., Sanders, T.A. and Ragsdale, C.W. (2001) Sonic Hedgehog control of size and shape in midbrain pattern formation.  Science 291, 2147-2150. Ragsdale, C.W. and Grove, E.A. (2001) Patterning the mammalian cerebral cortex.  Current Opinion in Neurobiology 11, 50-58.