Serrate/Notch Signaling Regulates the Size of the Progenitor Cell Pool inDrosophilaImaginal Rings

Abstract

imaginal rings are larval tissues composed of progenitor cells that are essential for the formation of adult foreguts, hindguts, and salivary glands. Specified from subsets of ectoderm in the embryo, imaginal ring cells are kept quiescent until midsecond larval instar, and undergo rapid proliferation during the third instar to attain adequate numbers of cells that will replace apoptotic larval tissues for adult organ formation. Here, we show that Notch signaling is activated in all three imaginal rings from middle embryonic stage to early pupal stage, and that Notch signaling positively controls cell proliferation in all three imaginal rings during the third larval instar. Our mutant clonal analysis, knockdown, and gain-of-function studies indicate that canonical Notch pathway components are involved in regulating the proliferation of these progenitor cells. Both -activation and-inhibition between the ligand and receptor control Notch activation in the imaginal ring. Serrate (Ser) is the ligand provided from neighboring imaginal ring cells that -activates Notch signaling, whereas both Ser and Delta (Dl) could-inhibit Notch activity when the ligand and the receptor are in the same cell. In addition, we show that Notch signaling expressed in middle embryonic and first larval stages is required for the initial size of imaginal rings. Taken together, these findings indicate that imaginal rings are excellent models to decipher how progenitor cell number and proliferation are developmentally regulated, and that Notch signaling in these imaginal tissues is the primary growth-promoting signal that controls the size of the progenitor cell pool.

Polyploid mitosis and depolyploidization promote chromosomal instability and tumor progression in a Notch-induced tumor model

“…In contrast, the TZ cells located at the posterior boundary of the ImR showed polyploidy, with three major peaks at 4C, 8C, and 16C of DNA content (Figures 1C and S1D). These findings suggest that the TZ cells are polyploid cells, different from their diploid anterior ImR neighbors and the polytene salivary gland cells (Yang and Deng, 2018).…”

“…Taken together, these findings suggest that the TZ cells undertake 2 to 3 rounds of endoreplication to become polyploid, different from their anterior neighbors that undergo rapid mitosis during the third larval instar (Yang and Deng, 2018).…”

“…Similar to imaginal disc cells, the ImR epithelial cells are precursors for adult structures. We found that Notch, an evolutionarily conserved pathway, controls the size of progenitor cell pool of the ImRs (Yang and Deng, 2018). At the TZ, there is a high level of endogenous Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and Jun N-terminal kinase (JNK) signaling activity, which makes this region a tissue tumor hotspot for oncogenic Notch-induced tumor formation (Tamori et al, 2016;Yang et al, 2019).…”

Alzheimer’s disease-associatedTM2Dgenes regulate Notch signaling and neuronal function inDrosophila

“…hsFLP; tub-Gal80 ts , FRT40A/CyO; tub-GAL4, UAS-GFP/TM6b, Tb (Yang and Deng, 2018) kuz e29-4 , FRT40A/CyO (Rooke et al, 1996) Flies were crossed and maintained at 25°C. First-instar larvae (36-48 hours after egg laying) were heat shocked for 40 minutes twice a day at 37°C.…”

Accelerated cell cycles enable organ regeneration under developmental time constraints in theDrosophilahindgut

“…As documented by Robertson over 80 years ago (Robertson, 1936), the larval ileum undergoes histolysis, and is replaced by regenerative activity from adult hindgut precursors. Cell division from the larval pylorus, which occurs during metamorphosis, is the source of the expanded adult pylorus, and also the new adult ileum (Cohen et al, 2020;Fox and Spradling, 2009;Sawyer et al, 2017;Takashima et al, 2008;Yang and Deng, 2018). This development is not disrupted by a severe, acute injury to the wandering 3 rd instar larval pylorus.…”