Linking the environment, DAF-7/TGFβ signaling and LAG-2/DSL ligand expression in the germline stem cell niche

Abstract

The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFβ signaling promotes expression of lag-2 in the DTC in a daf-3-dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the lag-2 promoter. We further identify a 25 bp DAF-3 binding element required for the DTC lag-2 reporter response to the environment and to DAF-7/TGFβ signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool.

PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus

“…Taken together, these results indicate that PGS/BMSCs facilitate regeneration of uterus due to the increase of vascularity which promotes the approach to nutrients and hormones through the secreting various growth factors, including bFGF and VEGF . In addition to inducing angiogenesis, BMSCs may facilitate tissue repair through secreting TGF‐β1 which is helpful to a resurgent microenvironment by weakening apoptosis, abating immune responses . BMSCs secreted IGF‐1 to facilitate the propagation and migration of the epithelial cells, which enabled quick epithelialization and wound‐healing …”

Transcriptomic Profiling of DAF-7/TGFβ Pathway Mutants in C. elegans

“…Many studies on the DAF-7 TGFβ pathway reinforce the currently accepted model between daf-3 and its upstream regulators, in which a phenotypic or genotypic change observed in daf-1 mutants is suppressed in daf-1; daf-3 double mutants, suggesting that daf-3 is epistatic to daf-1 [24][25][26]38]. These findings magnify the canonical DAF-7 signaling pathway and suggest that daf-1; daf-3 double mutant animals are more similar to wild type animals than to daf-1 mutants.…”

“…This relationship has been observed in many other functions of the pathway, some of which may be conserved in higher animals, including humans. In addition to dauer formation, DAF-7 in C. elegans has been shown to play a role in regulating the expression of AMPA-type glutamate receptor GLR-1 [22], the expression of chemoreceptors in amphid neurons [23], the expression of genes in the distal tip cell to modulate the germline stem cell niche [24,25], and the production of prostaglandins that are important for sperm guidance [26]. In addition to dauer formation, DAF-7 in C. elegans has been shown to play a role in regulating the expression of AMPA-type glutamate receptor GLR-1 [22], the expression of chemoreceptors in amphid neurons [23], the expression of genes in the distal tip cell to modulate the germline stem cell niche [24,25], and the production of prostaglandins that are important for sperm guidance [26].…”

Niche maintenance of germline stem cells inC. elegansmales

“…Male gonads contain one distal and one dorsal DTC, each of which caps adjacent germ cells and contains minimal processes. During hermaphrodite larval development, the DTC caps adjacent germ cells, but does not have detectable processes (BYRD et al 2014;LINDEN et al 2017;PEKAR et al 2017).…”