CHARACTERIZATION OF THE GENETIC PATHWAYS INVOLVED IN NEURONAL MIGRATION IN THE ZEBRAFISH FOREBRAIN

The brain contains many millions of nerve cells (neurons) which are connected with each other through highly complex but very precisely co-ordinated circuits. In order that all the right connections are made between different groups of neurons, then many events must occur correctly during embryonic development. For instance, the neurons must acquire correct identities as this information is needed for the cells to make appropriate connections with their correct partners. They must also project very long processes (termed axons) that extend through the central nervous system (CNS) and eventually make connections with these target cells. The generation of brain areas that perform different and highly specialized functions relies broadly on two mechanisms: the specification of locally born cells by signals that activate specific programs of differentiation, and the contribution of immigrant cells that provide the area with neurons that have different abilities and adopt different roles. The regulation of the type and number of neurons that migrate into various areas of the CNS are crucial aspects of brain maturation and several congenital brain disorders, such as lissencephaly, are known to result from incorrect migration of brain cells. In this proposal we aim to identify key molecules that regulate the ordered migration of brain cells, with the hope of providing information that can be used to understand, devise cures for, or prevent, the disastrous consequences of defective neuronal migration during development.