Developmental Research

Developmental neuroscience seeks to reveal how multipotential progenitor cells differentiate into specialized cell types, in particular neurons and glia; how these cells migrate and interact with each other to form specific nervous tissue structures; how they influence each others fate, and behavior; and how neuronal activity modulate their function.

a) NEURONS

One of our research interests concerns the mechanisms by which neural epithelial cells develop to form the cerebral cortex. Analyses of the sequence of events leading to the mature, carefully positioned neurons offer potential for furthering our understanding of disease mechanisms of developmental pathologies, such as congenital malformations and fetal alcohol syndrome. A particular strength of our faculty is the coordinated study of the development of the synaptic structure and microcircuitry of the auditory system, and of the role of factors in neurodegenerative diseases induced by acoustic overstimulation which aims at unveiling mechanisms that could be manipulated to stimulate neuronal repair and regeneration. Microscopic and molecular methods in cell culture experiments, transgenic mice, and transplantation of cultured neurons into the central nervous system further provide complementary models and a theoretical framework for exploring the cellular basis of critical periods in the differentiation of specific types of neurons and their connections.

b) GLIA

Oligodendrocytes produce the myelin sheath, a multilamellar membrane that envelops axons and is necessary for the salutatory conduction of nerve impulses. The development of oligodendrocytes is regulated by a plethora of environmental interactions, including numerous specific growth factors and cell adhesion molecules. After the oligodendrocyte progenitor becomes committed to a myelinating phenotype, the cell undergoes further regulated maturation leading to the production of the mature myelin membrane. These studies are essential to the development of strategies for enhancing oligodendrocyte production, and myelin repair in patients affected with conditions such as Multiple Sclerosis. Current interests of the faculty emphasize the regulation of oligodendrocyte development by fibroblast growth factor (FGF) and its family of receptors, molecular mechanisms of myelin biogenesis, and signal transduction in both oligodendrocytes and myelin.

Microglia are involved in the immune surveillance of the central nervous system. Current studies seek to expose the interactions of microglia with oligodendrocytes at early stages of development that may be essential in determining the pattern of immune response seen in adults when they are exposed to viral, bacterial, or self-antigen, such as the case may be in Multiple Sclerosis.

Astrocytes perform several functions in the central nervous system, and these functions vary as the brain develops and cell-cell interactions become highly specialized. One area of investigation concerns the mechanism by which astrocytes may signal oligodendrocytes to delineate the axonal territory that is to be myelinated. Astrocytes undergo changes in gene expression in several pathological conditions associated with chronic diseases, infections, or injury. A particular question being asked by our faculty is whether these changes represent a return to an early developmental stage that can contribute to repair of the nervous tissue.