ResponseEric5_6_2005.doc.docVIP

Dear Ted, We found the reviewers’ comments very helpful and thoroughly revised the manuscript accordingly. All changes made are highlighted. Most importantly: We got rid of former Figure 1, which (we agree with Reviewer II) was confusing; We added new Figures 4, 5 and 9. New figure 4 shows convincingly the co-localization of actin and dynein throughout the mitotic cycle (therefore we followed the suggestion of Reviewers II and III). New figure 5 combines former Ncd images from former figures 1 and 5. Figure 9 illustrates co-localization at the cortex of tubulin and actin throughout the mitotic cycle, which answers some of Reviewer III queries. Some of Reviewers II and III queries about experimental evidence for actin and dynein importance in spindle development are answered by previous published work – ours and by other groups. We made corresponding references. We respectfully disagree with the statement of Reviewer III that without direct forces’ measurements and map of dynein activity the model remains purely theoretical. At the present, it is impossible to do the suggested experiments, and the value of computational modeling is that it complements microscopy in a meaningful quantitative way by examining various scenario of spindle assembly and by indirectly estimating spindle forces. We carefully considered Reviewer III queries concerning nuclear deformations, MT asters’ asymmetry and role of Ncd and revised the text to make the meaning of the results more clear and to dispel what is, hopefully, just misunderstanding. Finally, we corrected the typos and answered in detail all Reviewers’ comments (below) making respective changes in the text. We hope that in the present form the manuscript is acceptable at MBOC. Sincerely, Alex Mogilner %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% Reviewer I: 1) The inclusion of reference to the “spindle matrix” in the abstract seems to indicate stronger support for this effect than is actually justified based on the results presented.