Mitotic chromosomes scale to nuclear-cytoplasmic ratio and cell size in Xenopus

Abstract
Data availability
Article and author information
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Abstract

During the rapid and reductive cleavage divisions of early embryogenesis, subcellular structures such as the nucleus and mitotic spindle scale to decreasing cell size. Mitotic chromosomes also decrease in size during development, presumably to scale coordinately with mitotic spindles, but underlying mechanisms are unclear. Here we combine in vivo and in vitro approaches using eggs and embryos from the frog Xenopus laevis to show that mitotic chromosome scaling is mechanistically distinct from other forms of subcellular scaling. We found that mitotic chromosomes scale continuously with cell, spindle and nuclear size in vivo. However, unlike for spindles and nuclei, mitotic chromosome size cannot be re-set by cytoplasmic factors from earlier developmental stages. In vitro, increasing nuclear-cytoplasmic (N/C) ratio is sufficient to recapitulate mitotic chromosome scaling, but not nuclear or spindle scaling, through differential loading of maternal factors during interphase. An additional pathway involving importin a scales mitotic chromosomes to cell surface area/volume ratio (SA/V) during metaphase. Finally, single-chromosome immunofluorescence and Hi-C data suggest that mitotic chromosomes shrink during embryogenesis through decreased recruitment of condensin I, resulting in major rearrangements of DNA loop architecture to accommodate the same amount of DNA on a shorter axis. Together, our findings demonstrate how mitotic chromosome size is set by spatially and temporally distinct developmental cues in the early embryo.

Data availability

Sequencing data have been deposited in GEO under the code GSE217111.

The following data sets were generated

1. Zhou CY
2. Dekker B
3. Liu M
4. Cabrera H
5. Ryan J
6. Dekker J
7. Heald R
(2022) Mitotic chromosomes scale to nucleo-cytoplasmic ratio and cell size in Xenopus
NCBI Gene Expression Omnibus, GSE217111.

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217111

Article and author information

Author details

Coral Y Zhou

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
coral.zhou@berkeley.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-7471-4645
Bastiaan Dekker

Department of Systems Biology, University of Massachusetts Medical School, Worcester, United States

Competing interests
No competing interests declared.
Ziyuan Liu

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Hilda Cabrera

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Joel Ryan

Advanced BioImaging Facility, McGill University, Montreal, Canada

Competing interests
No competing interests declared.
Job Dekker

Department of Systems Biology, University of Massachusetts Medical School, Worcester, United States

Competing interests
Job Dekker, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-5631-0698
Rebecca Heald

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
bheald@berkeley.edu

Competing interests
No competing interests declared.

Funding

National Institute of General Medical Sciences (R35GM118183)

Rebecca Heald

Jane Coffin Childs Memorial Fund for Medical Research

Coral Y Zhou

Howard Hughes Medical Institute

Job Dekker

National Human Genome Research Institute (HG003143)

Job Dekker

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was conducted within the guidelines for Care and Use of Laboratory Animals by the National Institutes of Health. All procedures were performed in accordance with our Animal Utilization Protocol (AUP-2014-08-6596-2) and under strict regulation by the UC-Berkeley Institutional Animal Care and Use Committee (IACUC, NIH Insurance #A4107-01).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.