Preprint
SYS-1/beta-catenin inheritance and regulation by Wnt-signaling during asymmetric cell division
bioRxiv
Cold Spring Harbor Laboratory
07/21/2023
DOI: 10.1101/2023.07.21.550069
PMCID: PMC10370182
PMID: 37503055
Abstract
Asymmetric cell division (ACD) allows daughter cells of a polarized mother to acquire different developmental fates. In
C. elegans
, the Wnt/β-catenin Asymmetry (WβA) pathway oversees 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
de novo
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 this accumulation is regulated via dynein trafficking. Photoconversion of the EMS cell during Wnt-driven ACD shows daughter cell inheritance of mother cell SYS-1. Additionally, loss of centrosomal SYS-1 increased inherited SYS-1 and, surprisingly, loss of centrosomal SYS-1 also resulted in increased levels of
de novo
SYS-1 in both EMS daughter cells. Lastly, we show that daughter cell negative regulation of SYS-1 via the destruction complex member APR-1/APC is key to limit both the
de novo
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 IowaBryan T. Phillips - University of Iowa
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- DOI
- 10.1101/2023.07.21.550069
- PMID
- 37503055
- PMCID
- PMC10370182
- Publisher
- Cold Spring Harbor Laboratory
- Language
- English
- Date posted
- 07/21/2023
- Academic Unit
- Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984448057702771
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