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Neurobiology

Introduction

Neurobiology, the newest department at TSRI, was established 1992 by a group of eleven distinguished scientists who brought their research program from the Rockefeller University in New York City to the Institute. Since that time, the program has grown significantly in both size and scope.

The major scientific focus of the Department is on vertebrate development, in particular, the development of the nervous system. An emphasis is placed on how the brain develops its "wiring" and functions to guide motion, perception and sensation.

The fundamental question of development is: How does the one-dimensional genetic code specify the cellular events that result in a three-dimensional animal of a given species? At present, there is no comprehensive theory to explain development in the same way that theories of evolution and genetics describe those phenomena. The availability of modern cellular and molecular biology tools, in recent decades, has given rise to a view of embryonic development that centers on the cell and the gene as fundamental units of development.

Researchers at TSRI are addressing this problem by focusing on the brain in the earliest stages of development. The role of specific adhesion molecules in regulating cell-cell and cell-matrix interactions is being examined in an effort to link information on genetic information to events that direct cell division, movement, and eventual death.

These efforts suggest a link between cell adhesion molecules (CAMs) that control cell-cell binding, and substrate adhesion molecules (SAMs), which affect cell migration and transformations of cell states. In the nervous system, CAMs and SAMs are known to facilitate, among other things, cell migration, neurite guidance and extension, and regeneration.

CAMs are essential for repair of the brain and nervous system following damage by trauma or disease, and mutations or disturbances of CAM expression can lead to various diseases, including congenital disorders. Recent research has even shown that one family of CAMs is the evolutionary basis for the structure and function of the entire immune system.

For normal development to take place, the expression of CAMs and SAMs is co-regulated by very precise genetic signaling. In an effort to understand, at the gene level, how CAMs and SAMs are regulated, TSRI researchers recently extended the scope of this research and identified promoters for the genes encoding the CAMs, N-CAM, L-CAM, Ng-CAM, and L1 and the SAM tenascin. It was subsequently shown that regions of each of these genes contained sequences that were regulated by homeobox genes -- DNA sequences that play an important role in embryonic development. This is the first demonstration that an adhesion molecule could be controlled by homeobox genes.

The Department also studies theories of how the brain functions in perception -- work of considerable significance in understanding memory loss, dyslexia, recovery from stroke, and learning disabilities in general.