PT  - JOURNAL ARTICLE
AU  - Suzanne E. M. van der Horst
AU  - Janine Cravo
AU  - Alison Woollard
AU  - Juliane Teapal
AU  - Sander van den Heuvel
TI  - <em>C. elegans</em> Runx/CBFβ suppresses POP-1(TCF) to convert asymmetric to proliferative division of stem cell-like seam cells
AID  - 10.1101/625335
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 625335
4099  - http://biorxiv.org/content/early/2019/05/03/625335.short
4100  - http://biorxiv.org/content/early/2019/05/03/625335.full
AB  - A correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight in the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by non-canonical Wnt/β-catenin asymmetry signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy, we show that symmetric cell divisions maintain the asymmetric localization of Wnt/β-catenin pathway components. Observations based on lineage-specific knockout and GFP-tagging of endogenous pop-1 support the model that POP-1TCF induces differentiation at a high nuclear level, while low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator rnt-1Runx and cofactor bro-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, opposition between the C. elegans Runx/CBFβ and TCF stem-cell regulators controls the switch between asymmetric and symmetric seam cell division.