MUTATIONS IN THE CELL-ADHESION MOLECULE LI CAUSE MENTAL-RETARDATION

Recently, studies in the usually disparate fields of human genetics an d developmental neurobiology have converged to reveal that some types of human mental retardation and brain malformations are due to mutatio ns that affect the neural cell adhesion molecule LI. LI has a very com plex biology, interacting with a variety of ligands, and functioning i n migration of neurons and growth of axons. Over the past few years, i t has also become clear that LI is able to influence intracellular sec ond messengers. The identification of a number of different mutations in LI, some of which alter the extracellular portion of the molecule, and others that change only the cytoplasmic tail, confirm that LI is a crucial player in normal brain development. The information gained fr om genetic analysis of human LI is giving new insights into how LI fun ctions in the formation of major axon pathways, but it also raises una nticipated questions about how LI participates in the development of c ortical and ventricular systems.