TY - JOUR
T1 - Acentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract
AU - Gouveia, Bernardo
AU - Setru, Sagar U.
AU - King, Matthew R.
AU - Hamlin, Aaron
AU - Stone, Howard A.
AU - Shaevitz, Joshua W.
AU - Petry, Sabine
N1 - Funding Information:
We thank Jake DeLuca, Keith DeLuca, and Jeanne Mick for the CENPA-GFP HeLa cell line, Kayoko Hayashihara, and Kiichi Fukui for helpful discussions regarding chromosome isolation, Nachama Sterm for assisting with chromosome counting in purified fractions, Venecia Valdez for the Eg5 antibody, Gary Laevsky and the Confocal Imaging Facility, and all members of the Petry, Shaevitz, and Stone labs for advice and input. B.G. was supported by PD Soros fellowship, NSF GRFP DGE-2039656, and Wallace Memorial Honorific Fellowship. S.U.S. was supported by NIH NCI NRSA 1F31CA236160 and NHGRI training grant 5T32HG003284. M.R.K. was supported by NIGMS training grant T32GM007388. This work was funded by NIH 1DP2GM123493, NIH R01 GM141100, Pew Scholars Program 00027340, Packard Foundation 201440376, CPBF NSF PHY-1734030, and Wilke Family Foundation/O’Brien Family Fund for Health Research.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Microtubules are generated at centrosomes, chromosomes, and within spindles during cell division. Whereas microtubule nucleation at the centrosome is well characterized, much remains unknown about where, when, and how microtubules are nucleated at chromosomes. To address these questions, we reconstitute microtubule nucleation from purified chromosomes in meiotic Xenopus egg extract and find that chromosomes alone can form spindles. We visualize microtubule nucleation near chromosomes using total internal reflection fluorescence microscopy to find that this occurs through branching microtubule nucleation. By inhibiting molecular motors, we find that the organization of the resultant polar branched networks is consistent with a theoretical model where the effectors for branching nucleation are released by chromosomes, forming a concentration gradient that spatially biases branching microtbule nucleation. In the presence of motors, these branched networks are ultimately organized into functional spindles, where the number of emergent spindle poles scales with the number of chromosomes and total chromatin area.
AB - Microtubules are generated at centrosomes, chromosomes, and within spindles during cell division. Whereas microtubule nucleation at the centrosome is well characterized, much remains unknown about where, when, and how microtubules are nucleated at chromosomes. To address these questions, we reconstitute microtubule nucleation from purified chromosomes in meiotic Xenopus egg extract and find that chromosomes alone can form spindles. We visualize microtubule nucleation near chromosomes using total internal reflection fluorescence microscopy to find that this occurs through branching microtubule nucleation. By inhibiting molecular motors, we find that the organization of the resultant polar branched networks is consistent with a theoretical model where the effectors for branching nucleation are released by chromosomes, forming a concentration gradient that spatially biases branching microtbule nucleation. In the presence of motors, these branched networks are ultimately organized into functional spindles, where the number of emergent spindle poles scales with the number of chromosomes and total chromatin area.
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U2 - 10.1038/s41467-023-39041-z
DO - 10.1038/s41467-023-39041-z
M3 - Article
C2 - 37344488
AN - SCOPUS:85162917997
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3696
ER -