The role of the Enhancer of split complex during cell fate determination in Drosophila

Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 139-148 ◽  
Author(s):  
Fred Tata ◽  
David A. Hartley

Molecular and genetic data predict that the Enhancer of split locus functions at the end of a pathway dictating appropriate cell fate determination in a number of developmental contexts. We have sought to dissect the role individual member genes of the complex play through a molecular analysis. Of the two principle class of genes, the first, members of the basic helix-loop-helix (bHLH) class of proteins are expressed in specific regions of the embryo in subtle, overlapping patterns in cells that will differentiate as epidermis. The second, groucho, a member of the WD40 class of proteins, is expressed more generally. Immunoprecipitation experiments do not implicate groucho in G protein mediated signal transduction, a known function of many WD40 type proteins. Instead, the nuclear localisation of the protein suggests a relationship to the bHLH members of the complex. Differences in expression of the bHLH genes between neurogenic mutants implies two pathways to their activation during epidermal determination.

2015 ◽  
Vol 112 (5) ◽  
pp. E402-E409 ◽  
Author(s):  
Marcelo Boareto ◽  
Mohit Kumar Jolly ◽  
Mingyang Lu ◽  
José N. Onuchic ◽  
Cecilia Clementi ◽  
...  

Notch signaling pathway mediates cell-fate determination during embryonic development, wound healing, and tumorigenesis. This pathway is activated when the ligand Delta or the ligand Jagged of one cell interacts with the Notch receptor of its neighboring cell, releasing the Notch Intracellular Domain (NICD) that activates many downstream target genes. NICD affects ligand production asymmetrically––it represses Delta, but activates Jagged. Although the dynamical role of Notch–Jagged signaling remains elusive, it is widely recognized that Notch–Delta signaling behaves as an intercellular toggle switch, giving rise to two distinct fates that neighboring cells adopt––Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Here, we devise a specific theoretical framework that incorporates both Delta and Jagged in Notch signaling circuit to explore the functional role of Jagged in cell-fate determination. We find that the asymmetric effect of NICD renders the circuit to behave as a three-way switch, giving rise to an additional state––a hybrid Sender/Receiver (medium ligand, medium receptor). This phenotype allows neighboring cells to both send and receive signals, thereby attaining similar fates. We also show that due to the asymmetric effect of the glycosyltransferase Fringe, different outcomes are generated depending on which ligand is dominant: Delta-mediated signaling drives neighboring cells to have an opposite fate; Jagged-mediated signaling drives the cell to maintain a similar fate to that of its neighbor. We elucidate the role of Jagged in cell-fate determination and discuss its possible implications in understanding tumor–stroma cross-talk, which frequently entails Notch–Jagged communication.


Nature ◽  
2002 ◽  
Vol 416 (6883) ◽  
pp. 854-860 ◽  
Author(s):  
Emi K. Nishimura ◽  
Siobhán A. Jordan ◽  
Hideo Oshima ◽  
Hisahiro Yoshida ◽  
Masatake Osawa ◽  
...  

2016 ◽  
Vol 104 (3) ◽  
pp. 324-329 ◽  
Author(s):  
Shin’ichiro Yasunaga ◽  
Yoshinori Ohno ◽  
Naoto Shirasu ◽  
Bo Zhang ◽  
Kyoko Suzuki-Takedachi ◽  
...  

2014 ◽  
Vol 26 (2) ◽  
pp. 186-191 ◽  
Author(s):  
Jin Hao ◽  
Yueling Zhang ◽  
Yating Wang ◽  
Rui Ye ◽  
Jingyi Qiu ◽  
...  

Epigenetics ◽  
2013 ◽  
Vol 9 (1) ◽  
pp. 90-100 ◽  
Author(s):  
Miguel Alejandro Lopez-Ramirez ◽  
Stefania Nicoli

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