Axons grow out along predictable routes to specific destinations. An EM study of the early development of one of the main chick wing nerves - the interosseous nerve - helps to show how they do it. The growing tip of the nerve appears frayed, consisting of nerve fibres occurring singly or in small bundles, taking slightly divergent paths. Most of these pioneer nerve fibres have the characteristic appearance of growth cones. They are not seen to advance along fibrils of the intercellular matrix (as one might expect from some tissue culture experiments), but instead are generally in close contact over their whole surface either with mesenchyme cells or with other nerve fibres. The same is true of the axons at more proximal levels of the developing nerve: they too are never naked, but always in contact either with other axons or with mesenchyme cells. Later nerve fibres follow the pioneers: their growth cones travel out in contact with the pre-existing axons, within the primitive perineurium formed by the enveloping mesenchyme cells, and most often close to the periphery of the fascicle.
Pioneer growth cones in virgin mesenchyme: an electron-microscope study in the developing chick wing
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L. K. Al-Ghaith, J. H. Lewis; Pioneer growth cones in virgin mesenchyme: an electron-microscope study in the developing chick wing. Development 1 April 1982; 68 (1): 149–160. doi: https://doi.org/10.1242/dev.68.1.149
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