Cell Polarity and Asymmetric Cell Division by the Wnt Morphogen

Centrosomal Enrichment and Proteasomal Degradation of SYS-1/β-catenin Requires the Microtubule Motor Dynein

“…Having established a two-fold role for SYS-1 regulation in microtubule-mediated trafficking, we investigated the role microtubule trafficking played in regulating SYS-1 dependent cell fate decisions. Since the SYS-1 centrosomal localization pattern has been seen across all examined SYS-1-expressing tissues (Phillips, Kimble et al 2007; Huang, Lin et al 2007; Baldwin and Phillips 2018; Lam and Phillips 2017), we investigated cell fate changes in embryonic and larval tissues across one embryonic and two larval SYS-1 dependent cell fate decisions. These included the transcriptional reporter of the WβA target gene, end-1, in the establishment of SYS-1 dependent endoderm, and an anatomical marker for larval specification of the stem cell-like cells of the hypodermal seam and the germline stem cell niche.…”

“…We also investigated larval ACDs to determine the effect that extra transcriptionally active SYS-1 has on organismal development. We examined the seam cells (SCs) and distal tip cells (DTCs) because of their sensitivity to SYS-1 dependent gene activation (Baldwin, Phillips et al 2016; Baldwin and Phillips 2018; Lam and Phillips 2017; Mila, Putzke et al 2015). In wild-type animals, DTC lineages undergo asymmetric cell division during L1 to give rise to two DTCs, while sys-1 mutants and animals overexpressing SYS-1 show loss or gain of DTCs, respectively, due to symmetric cell division (Fig 6A) (Miskowski, Kimble et al 2001; Siegfried, Kimble et al 2004; Kidd, Kimble et al 2005; Chesney, Kimble et al 2009).…”

“…Here we focus specifically on the C. elegans β-catenin SYS-1 for its role as a transcriptional co-activator in a modified Wnt/β-cat signaling pathway, the Wnt/β-catenin Asymmetry pathway(WβA) (Phillips, Kimble et al 2007). The WβA pathway is a specialized application of the more basic Wnt signaling paradigm, wherein regulation of the co-activator SYS-1 (β-catenin) modulates the activity of transcription factor POP-1 (TCF), during asymmetric cell division (Baldwin and Phillips 2018, Lam and Phillips 2017). Mother cells undergoing a WβA-driven division polarize components of the Wnt signaling pathway along the axis of the division – distributing positive regulators of a Wnt response, the Frizzled receptor and downstream effector Disheveled, to the signaled pole of the cell, and negative regulators, members of the β-Catenin destruction complex APC and Axin, to the unsignaled pole (Baldwin and Phillips 2014; Baldwin, Phillips et al 2016; Sugioka, Sawa et al 2011; Mizumoto and Sawa, 2007).…”