Deconvolving the roles of Wnt ligands and receptors in sensing and amplification

Molecular Systems Biology

Rui Zhen Tan¹  Ni Ji³  Remco A Mentink²  Hendrik C Korswagen² 

[1] Harvard University Graduate Biophysics Program, Harvard Medical School, Boston, MA, USA;Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, The Netherlands;Department of Brian and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA

关键词: Caenorhabditis elegans;    cell polarity;    phenomenological modeling;    Wnt signaling;   

DOI  :  10.1038/msb.2012.64

来源: Wiley

【 摘 要 】

Abstract

Establishment of cell polarity is crucial for many biological processes including cell migration and asymmetric cell division. The establishment of cell polarity consists of two sequential processes: an external gradient is first sensed and then the resulting signal is amplified and maintained by intracellular signaling networks usually using positive feedback regulation. Generally, these two processes are intertwined and it is challenging to determine which proteins contribute to the sensing or amplification process, particularly in multicellular organisms. Here, we integrated phenomenological modeling with quantitative single-cell measurements to separate the sensing and amplification components of Wnt ligands and receptors during establishment of polarity of the Caenorhabditis elegans P cells. By systematically exploring how P-cell polarity is altered in Wnt ligand and receptor mutants, we inferred that ligands predominantly affect the sensing process, whereas receptors are needed for both sensing and amplification. This integrated approach is generally applicable to other systems and will facilitate decoupling of the different layers of signal sensing and amplification.

Synopsis

Establishment of cell polarity involves sensing of external cues followed by signal amplification. Analysis of Caenorhabditis elegans P-cell polarity in Wnt ligand and receptor mutants is used to separate the contribution of ligands and receptors to the sensing and amplification processes.

• By combining quantitative single molecule transcript counting with phenomenological modeling, we studied the effects of ligand and receptor loss on P cells’ division in Caenorhabditis elegans.
• We found that loss of ligands leads to polarity reversals whereas polarity loss is observed in the receptor mutants.
• These results suggest that ligands affect primarily the sensing process whereas receptors are needed for both sensing and amplification.
• Our integrated approach is generally applicable to other systems and will facilitate decoupling of the different layers of signal sensing and amplification.

【 授权许可】

CC BY-NC-SA   
Copyright © 2013 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.