Journal article
SYS-1/beta-catenin inheritance and regulation by Wnt-signaling during asymmetric cell division
Molecular biology of the cell, Vol.36(3), ar25
03/01/2025
DOI: 10.1091/mbc.E24-10-0441
PMCID: PMC11974967
PMID: 39813084
Abstract
Asymmetric cell division (ACD) allows daughter cells of a polarized mother to acquire different developmental fates. In
, the Wnt/β-catenin Asymmetry (WβA) pathway regulates many embryonic and larval ACDs; here, a Wnt gradient induces an asymmetric distribution of Wnt signaling components within the dividing mother cell. One terminal nuclear effector of the WβA pathway is the transcriptional activator SYS-1/β-catenin. SYS-1 is sequentially negatively regulated during ACD; first by centrosomal regulation and subsequent proteasomal degradation and second by asymmetric activity of the β-catenin "destruction complex" in one of the two daughter cells, which decreases SYS-1 levels in the absence of WβA signaling. However, the extent to which mother cell SYS-1 influences cell fate decisions of the daughters is unknown. Here, we quantify inherited SYS-1 in the differentiating daughter cells and the role of SYS-1 inheritance in Wnt-directed ACD. Photobleaching experiments demonstrate the GFP::SYS-1 present in daughter cell nuclei is comprised of inherited and
translated SYS-1 pools. We used a photoconvertible DENDRA2::SYS-1, to directly observe the dynamics of inherited SYS-1. Photoconversion during mitosis reveals that SYS-1 clearance at the centrosome preferentially degrades older SYS-1 and that newly localized centrosomal SYS-1 depends on dynein trafficking. Photoconversion of DENDRA2::SYS-1 in the EMS cell during Wnt-driven ACD shows daughter cell inheritance of mother cell SYS-1. Additionally, disrupting centrosomal SYS-1 localization in mother cells increased inherited SYS-1 and, surprisingly, loss of centrosomal SYS-1 also resulted in increased levels of
SYS-1 in both EMS daughter cells. Lastly, we show that negative regulation of SYS-1 in daughter cells via the destruction complex member APR-1/APC is key to limit both the
and the inherited SYS-1 pools in both the E and the MS cells. We conclude that regulation of both inherited and newly translated SYS-1 via centrosomal processing in the mother cell and daughter cell regulation via Wnt signaling are critical to maintain sister SYS-1 asymmetry during ACD.
Details
- Title: Subtitle
- SYS-1/beta-catenin inheritance and regulation by Wnt-signaling during asymmetric cell division
- Creators
- Maria F Valdes Michel - University of Iowa, Ophthalmology and Visual SciencesBryan T Phillips - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.36(3), ar25
- DOI
- 10.1091/mbc.E24-10-0441
- PMID
- 39813084
- PMCID
- PMC11974967
- NLM abbreviation
- Mol Biol Cell
- ISSN
- 1939-4586
- eISSN
- 1939-4586
- Publisher
- AMER SOC CELL BIOLOGY
- Grant note
- National Institutes of Health (NIH) Office of Research Infrastructure ProgramsNIH: RO1GM114007 University of Iowa Graduate College Fellowships
We thank members of the Phillips lab for comments on the manuscript. Strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH) Office of Research Infrastructure Programs (P40 OD01440). We also want to thank the Carver Center for Imaging at the University of Iowa and its director, Dr. Michael Dailey. This work was supported by NIH award RO1GM114007 (to B.T.P), and University of Iowa Graduate College Fellowships to M.V.
- Language
- English
- Electronic publication date
- 01/15/2025
- Date published
- 03/01/2025
- Academic Unit
- Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984773415402771
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