PgmNr D185: The ecdysone and JAK/STAT pathways regulate proper morphogenetic movement of squamous cells by suppressing Notch-induced Broad.

Authors:
Dongyu Jia 1 ; Allison Jevitt 1 ; Yoichiro Tamori 2 ; Yi-Chun Huang 1 ; Gabriel Calvin 1 ; Wu-Min Deng 1


Institutes
1) Florida State University, Tallahassee, FL, USA; 2) National Institute of Genetics, Mishima, Japan.


Keyword: cancer

Abstract:

During development, proper formation of epithelial tissues is critical for normal cellular functions, and improper morphological changes could potentially contribute to tumor malignancy. To study epithelial morphogenesis, many animal models have been established, and the Drosophila egg chamber is one important system to understand morphogenetic movements. Epithelial cells have three major shapes: cuboidal, columnar and squamous.  Here, we focus on squamous cells (SCs, also known as stretched cells), which are restricted at the surface of anterior egg chambers in cuboidal shape at the beginning, then rapidly become flattened in twelve hours to spread over half of the surface. The regulation of this drastic morphological change is still unclear. Our report indicates Broad (Br) interacts with the Notch, ecdysone and JAK/STAT pathways, serving as an important spatiotemporal cue for proper cell differentiation, elongation and movement. The early uniform pattern of Br in the follicular epithelium is directly established by Notch signaling at stages 5/6 during Drosophila oogenesis. Ecdysone and JAK/STAT signaling synergize to suppress Br in SCs to de-repress themselves from stage 8 to 10a, which contributes to proper SC stretching. During the process, ecdysone signaling is essential for initiation of SC stretching, while JAK/STAT regulates SCs distribution and cell fate determination. Our findings also shed new light on understanding of squamous cell carcinomas (SCCs), as the SC stretching process is accompanied by loss of epithelial cell marker, and our meta-analysis results implicate that human homologs of ecdysone and JAK/STAT are associated with patient survival outcomes in SCCs.



Flybase Genetic Index:
1. FlyBase gene symbol: N; FBgn: 0004647
2. FlyBase gene symbol: EcR; FBgn: 0000546
3. FlyBase gene symbol: Stat92E; FBgn: 0016917
4. FlyBase gene symbol: br; FBgn: 0283451