RRC ID 59616
Author van der Horst SEM, Cravo J, Woollard A, Teapal J, van den Heuvel S.
Title C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells.
Journal Development
Abstract 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 into 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 divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our 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, whereas 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, we found that conserved Runx/CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.
Volume 146(22)
Published 2019-11-18
DOI 10.1242/dev.180034
PII dev.180034
PMID 31740621
PMC PMC6899014
MeSH Alleles Animals Asymmetric Cell Division CRISPR-Cas Systems Caenorhabditis elegans / cytology* Caenorhabditis elegans Proteins / metabolism* Cell Differentiation Cell Division Cell Lineage Cell Proliferation Core Binding Factor beta Subunit / metabolism* DNA-Binding Proteins / metabolism* Down-Regulation Gene Expression Regulation, Developmental Green Fluorescent Proteins / metabolism High Mobility Group Proteins / metabolism* Male RNA Interference Repressor Proteins / metabolism Stem Cells / cytology* Transcription Factors / metabolism* Wnt Signaling Pathway
IF 5.763
Times Cited 2
C.elegans tm388 tm1183