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Hideki ENOMOTO, M. D., Ph. D. 
The
architecture of the neural system, which underlies much of the dynamism
of animal life, is frequently described as complex, but closer examination
reveals great beauty as well. The construction of this exquisite and elaborate
structure involves the birth, growth and death of countless individual
cells and is regulated by intercellular communication and cooperative
activity.
Our
laboratory is interested in questions fundamental to the development of
the nervous system: determining the specific extracellular signals and
cell autonomous routines that participate in the processes of neural development,
and resolving the means by which diverse families of signaling molecules
coordinate and interact at the molecular and cellular levels. To address
these questions, we focus on a class of signaling molecules known as neurotrophic
factors, most particularly, the GDNF Family Ligands (the GFLs). This family
of neurotrophic factors includes four known members – GDNF (for Glial
cell line Derived Neurotrophic Factor), Neurturin, Artemin and Persephin.
The GFLs signal via receptor complexes formed by the RET receptor tyrosine
kinase and one of four co-receptors, GRFα1-4. In vitro, these four receptors
show differential affinities for specific GFLs, with GFRα1 showing the
greatest ability to interact with the range of GFL family members. GFL
signaling has been shown to affect neuronal growth and migration as well
as axon guidance, and defects in this signaling system have been implicated
in a number of congenital health problems.
Our efforts will focus on the analysis of the physiological roles of neurotrophic factors, which we hope will lead to an improved understanding of the molecular bases of neural development, differentiation and pathology, and ultimately to potential clinical applications in the treatment of nervous system trauma and disease.
