Background: Breaking cell symmetry, known as polarization, requires dynamic reorganization of microtubules (MTs) and is essential to many cellular processes, including axon formation in neurons. A critical step in polarization is believed to be the "selective stabilization" of MTs, which hypothesizes a spatial and/or temporal shift toward net MT assembly in a preferred direction of growth. Results: We now find that a simpler "length-dependent" model, in which MT assembly parameters are spatially and temporally constant, predicts MT accumulation in the direction of growth because of longer mean first passage times in the longer direction. We experimentally tested both models by tracking MT assembly dynamics in polarizing embryonic chick forebrain neurons, and we confirmed that assembly is spatially and temporally constant during axon formation. Conclusion: Cell polarization occurs most simply through cell-length-dependent accumulation of MTs without MT stabilization or capture. In this way, F-actin-mediated cell shape and size changes can be read out by dynamic MTs undergoing simple dynamic instability to ultimately break cell symmetry.
Bibliographical noteFunding Information:
Thanks to M.G. Blackmore, J.L. Harder, and N. Koyano for assistance with in ovo electroporation and M.K. Gardner and C.E. Chan for assistance with MATLAB. Thanks to L. Cassimeris, P.C. Letourneau, and R.Y. Tsien for the plasmid gifts. We also thank P.C. Letourneau, B. Marsick, and D. Bray for helpful discussions. Supported by National Science Foundation grant MCB-0615568.