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.
Bibliographical noteFunding Information:
We thank Michael Hortsch for help with theaffinity purification of fasciclin IV protein and Mark Seeger for help with the S2 transfection experiments. This work was supported by Damon Runyon and Howard Hughes Medical Institute postdoctoral fellowships toA. L. K., by a National Institutesof Health predoctoral traineeship to D. J. M., by a National Science Foundation award to T. P. O., by an NIH Javits Award to D. B., and by the HHMI to C. S. C. This paper is dedicated to the memory of Tom Elkins.
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