Timothy O'connor

Fasciclin IV: Sequence, expression, and function during growth cone guidance in the grasshopper embryo

Monoclonal antibody 6F8 was used to characterize and clone fasciclin IV, a new axonal glycoprotein in the grasshopper, and to study its function during growth cone guidance. Fasciclin IV is dynamically expressed on a subset of axon pathways in the developing CNS and on circumferential bands of epithelial cells in developing limb buds. One of these bands corresponds to the location where the growth cones of the Ti1 pioneer neurons make a characteristic turn while extending toward the CNS. Embryos cultured in the 6F8 antibody or Fab exhibit aberrant formation of this axon pathway. cDNA sequence analysis suggests that fasciclin IV has a signal sequence; long extracellular, transmembrane, and short cytoplasmic domains; and shows no homology with any protein in the available data bases. Thus, fasciclin IV appears to be a novel integral membrane protein that functions in growth cone guidance.

Cytoskeletal events in growth cone steering

Oriented neural outgrowth is dependent upon the capability of growth cones to reorient the direction of their migration in response to contact with guidance information. Recent observations have directed attention toward the role of actin distribution and concentration in transmitting localized peripheral signals to central elements of the growth cone, particularly microtubules.