Kathryn W. Tosney

    Growth Cone Motility:

    The Control of Lamellar Extension

     

 

The motile organ of the axon, the growth cone, exends two types of cellular projections. Long cylindrical projections containing long actin filaments are the filopodia. Filopodia are essential for the extension of the second motile projection, thin, flat lamellae or 'veils' with short branched actin. Veils advance only between pairs of filopodia.

One way to control growth cone advance is to control veil motility. If a local guidance cue suppresses veils on one side of the growth cone, the growth cone will turn away from that cue. Conversely, if a cue induces veils on one side, cytoplasm will subsequently flow into the veil, advancing the growth cone on that side. Control of veil extension is a major guidance mechanism (Oakley and Tosney, 1993; Steketee et al., 1999).

We have discovered an intimate relationship between veil activities and a functionally distinct adhesion, shaft adhesions. These adhesions develop along the shafts of some but not all filopodia. They are functionally distinct from the basal adhesion, at the base of all filopodia, which regulates filopodial rather than veil projection (Steketee and Tosney, 2002; Steketee et al. 2001).

The advance of veils is controlled by shaft adhesions. Veils readily advance along those filopodia that lack shaft adhesions, but rarely extend along those filopodia that displayed shaft adhesions.
Experimental manipulation confirms that these adhesions inhibit veil advance. When adhesions are directly reduced using anti-laminin antibodies, the extent of veil advance and the proportion of filopodia lacking shaft adhesions both increase, in accord with a direct relationship.

veils

This relation between shaft adesions and veil advance is the target of important guidance cues. These cues are detected by adhesion of the filopodial tip. When a cellular cue (such as a Schwann cell or sclerotome cell) is contacted by a filopodial tip, veil extension and adhesions along the filopodial shaft alter in concert. Contact with a Schwann cell induces veil advance and prohibits shaft adhesions. In contrast, contact with a posterior sclerotome cell prohibits veil advance and promots shaft adhesions. In both cases, a signal propagated from the contacting filopodial tip alters the ability of the filopodial shaft to adhere to laminin.

These results show that veil extension is controlled by shaft adhesions. Moveover, guidance signal cascades can alter veil extension by altering shaft adhesions.

cells control veils

Publications

  • Steketee, M., and K.W. Tosney (2002) Three Functionally Distinct Adhesions in Filopodia: Shaft Adhesions Control Lamellar Extension, J. Neurosci., 22: 8071-8083
  • Steketee, M and KW Tosney (1999). Contact with isolated sclerotome cells steers sensory growth cones by altering distinct elements of extension. J. Neurosci. 19: 3495-3506.