Insight into Notch Signaling Steps That Involve pecanex from Dominant-Modifier Screens in Drosophila

Abstract

Notch signaling plays crucial roles in intercellular communications. In , the () gene, which encodes an evolutionarily conserved multi-pass transmembrane protein, appears to be required to activate Notch signaling in some contexts, especially during neuroblast segregation in the neuroectoderm. Although Pcx has been suggested to contribute to endoplasmic reticulum homeostasis, its functions remain unknown. Here, to elucidate these roles, we performed genetic modifier screens of We found that heterozygotes lacking its maternal contribution exhibit cold-sensitive lethality, which is attributed to a reduction in Notch signaling at decreased temperatures. Using sets of deletions that uncover most of the second and third chromosomes, we identified four enhancers and two suppressors of the cold-sensitive lethality. Among these, five genes encode known Notch-signaling components:, (), (), (), a member of the () family, and (). We showed that suppresses Dl endocytosis during neuroblast segregation in the neuroectoderm, as family genes reportedly do in the mesoderm for mesectoderm specification. Analyses of , a key regulator of vesicular fusion, suggested a novel role in neuroblast segregation, which is distinct from Nsf2's previously reported role in imaginal tissues. Finally,, which encodes a potential transcription factor, may play a role in Notch signaling during neuroblast segregation. These results reveal new research avenues for Pcx functions and Notch signaling.

Long Non-coding RNA Expression Profiling Identifies a Four-Long Non-coding RNA Prognostic Signature for Isocitrate Dehydrogenase Mutant Glioma

“…Notch signaling system, which plays important roles in human development, tissue homeostasis, and disease, is a highly conserved and wellcharacterized pathway. JAG1 is one of five canonical ligands in Notch signaling pathway expressed by mammalian cells (14,15). Jag1/Notch axis participated in tumorigenesis and in promoting the progression of colorectal cancer (16), ovarian cancer (17), and cancer stem cell (18).…”

Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association

“…This gene is highly conserved among species. Although its role in mammals is not well known, it has been studied in Drosophila, demonstrating that it is related to the NOTCH signaling pathway and may play a role in vesicular transport during neuroblast segregation of the neuroectoderm [Yamakawa et al, 2018. The NOTCH signaling pathway is known to be involved in the formation of anatomical structures affected in VAC-TERL association, such as the development of the cardiovascular system and the spine [Stevenson and Hunter, 2013].…”

Notch Signalling Under Maternal-to-Zygotic Transition

“…To identify genes cooperatively functioning with pcx , a genetic screen was conducted, which involved a cold-sensitive lethality of the pcx maternal/zygotic null [ 56 ]. Various gene components of Notch signaling, such as Delta, bib , and neur , were identified as enhancers and suppressors of lethality, suggesting that the screen fulfilled its purpose.…”

“…Various gene components of Notch signaling, such as Delta, bib , and neur , were identified as enhancers and suppressors of lethality, suggesting that the screen fulfilled its purpose. As a dominant suppressor, N-ethylmaleimide-sensitive factor 2 ( Nsf2 ), encoding a key regulator of vesicular fusion, was isolated from the screen [ 56 ]. NSF is known to control the cohesion of ER [ 64 , 65 ].…”

“…NSF is known to control the cohesion of ER [ 64 , 65 ]. Considering that the loss of the pcx function induces ER enlargement, Nsf2 and pcx may be antagonistic in the homoeostasis of ER morphology [ 56 ].…”