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Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans
Ngan Lam1, Michael A Chesney, Judith Kimble
1Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Abstract:
Wnt signaling regulates many aspects of metazoan development, including stem cells. In C. elegans, Wnt/MAPK signaling controls asymmetric divisions. A recent model proposed that the POP-1/TCF DNA binding protein works together with SYS-1/beta-catenin to activate transcription of target genes in response to Wnt/MAPK signaling. The somatic gonadal precursor (SGP) divides asymmetrically to generate distal and proximal daughters of distinct fates: only its distal daughter generates a distal tip cell (DTC), which is required for stem cell maintenance. No DTCs are produced in the absence of POP-1/TCF or SYS-1/beta-catenin, and extra DTCs are made upon overexpression of SYS-1/beta-catenin. Here we report that POP-1/TCF and SYS-1/beta-catenin directly activate transcription of ceh-22/nkx2.5 isoforms in SGP distal daughters, a finding that confirms the proposed model of Wnt/MAPK signaling. In addition, we demonstrate that the CEH-22/Nkx2.5 homeodomain transcription factor is a key regulator of DTC specification. We speculate that these conserved molecular regulators of the DTC niche in nematodes may provide insight into specification of stem cell niches more broadly.
Insights
Wnt signaling controls cell division in C. elegans. POP-1/TCF and SYS-1/beta-catenin activate ceh-22 gene expression, which is crucial for specifying stem cell niches.
Area of Science:
- Developmental biology
- Stem cell biology
- Molecular genetics
Background:
- Wnt signaling is vital for metazoan development and stem cell regulation.
- In C. elegans, Wnt/MAPK signaling governs asymmetric cell divisions.
- A model suggests POP-1/TCF and SYS-1/beta-catenin mediate Wnt/MAPK transcriptional responses.
Purpose of the Study:
- To investigate the role of POP-1/TCF and SYS-1/beta-catenin in regulating target gene transcription in C. elegans.
- To confirm the proposed model of Wnt/MAPK signaling in asymmetric cell divisions.
- To elucidate the function of CEH-22/Nkx2.5 in distal tip cell (DTC) specification.
Main Methods:
- Analysis of gene expression in C. elegans.
- Investigating the interaction of transcription factors POP-1/TCF and SYS-1/beta-catenin.
- Studying the role of ceh-22/nkx2.5 in DTC formation.
Main Results:
- POP-1/TCF and SYS-1/beta-catenin directly activate transcription of ceh-22/nkx2.5 isoforms in somatic gonadal precursor (SGP) distal daughters.
- This finding supports the proposed model of Wnt/MAPK signaling.
- CEH-22/Nkx2.5 is identified as a key regulator of DTC specification.
Conclusions:
- The study confirms the model of Wnt/MAPK signaling involving POP-1/TCF and SYS-1/beta-catenin.
- CEH-22/Nkx2.5 plays a critical role in specifying the distal tip cell niche.
- These conserved regulators may offer insights into broader stem cell niche specification mechanisms.
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