21 Cell and Growth Cone Migrations

Abstract

I. INTRODUCTION
During morphogenesis, some cells migrate from their origins to distant locations. The complex, stereotyped migrations of axonal growth cones, for example, determine the connectivity of the nervous system. Motile cells and processes can undergo directed movements in response to spatially patterned molecules (Keynes and Cook 1995; Garrity and Zipursky 1995), and recent studies suggest that specific directional cues are conserved from nematodes to chordates (Hedgecock et al. 1990; Ishii et al. 1992; Kennedy et al. 1994; Serafini et al. 1994; Colamarino and Tessier-Lavigne 1995).

Migrating cells may follow several different directional cues, often in strict sequence, during development. Moreover, they may halt migration at stereotyped positions or times either to divide or to differentiate. These changes in cell movements must reflect changes in the extracellular environment or changes within the motile cell itself. For example, cells might be constitutively responsive to multiple directional cues, changing course whenever they encounter a further cue within their repertoire. Instead, it appears that cells become responsive to new cues, or unresponsive to current ones, during the course of migration. Some transitions could be entirely autonomous, reflecting, for example, an intracellular clock, but many are contingent upon extracellular signals encountered during the course of migration. These transitions often involve new gene expression. Analysis of these transitions has identified signaling pathways and transcriptional cascades within migrating cells that help select substrate and direction of migration, or regulate transitions between motile and stationary states. One such pathway in nematodes responds to hormonal signals that advance...