Biology subjects

Gumienny, T. L.

Publications and source records attributed to Gumienny, T. L..

3 recordsLinked to original sources

bioRxiv2026

DBL-1/BMP signaling pathway Smads and master transcription regulator BLMP-1/PRDM1 interact to regulate organismal traits in Caenorhabditis elegans

Transforming Growth Factor beta (TGF-{beta}) signaling helps orchestrate multiple organismal traits in animals by regulating target gene expression. However, how this pathway's transcriptional regulators, called Smads, control target gene expression to generate different traits is not well understood. Using the C. elegans system, we identified the master chromatin remodeler B-lymphocyte maturation protein-1 (BLMP-1, a Kruppel-like zinc finger protein homologous to human PRDM1/BLIMP1) as a partner in Smad-mediated gene expression regulation. Previous research showed BLMP-1/PRDM1 controls organismal traits that the C. elegans TGF-{beta} superfamily member DBL-1 also affects. We identified genetic interactions between the DBL-1 pathway and blmp-1 for these traits. While BLMP-1/PRDM1 and DBL-1 pathway signaling had an additive effect on body size, blmp-1 mutants were epistatic to DBL-1 pathway mutants for male tail development, hermaphrodite gonad development, brood size, lipid levels, movement, and survival traits. We showed DBL-1 signaling transcriptionally regulates blmp-1 expression. We also identified a physical interaction between the DBL-1 pathway Smads and BLMP-1/PRDM1 using yeast-two hybrid analyses. Using bioinformatics and qPCR analysis, we showed that Smads and BLMP-1/PRDM1 regulate expression of common downstream target genes. Our work identifies novel interactions between the DBL-1 signaling pathway and BLMP-1, two conserved major transcriptional regulators, that ultimately influence a spectrum of organismal traits. We propose a model whereby BLMP-1/PRDM1 regulates DBL-1 signaling by acting as a gatekeeper, remodeling the chromatin architecture to control the access of the Smad complex to target genes. Together, our results reveal a direct link between a TGF-{beta} signaling pathway and a PRDM1-family master transcription regulator and offer clues to how they interact to control larval and adult traits. Our work suggests a conserved mechanism of transcriptional control of developmental traits by the Smad-PRDM axis.

genetics↗

bioRxiv2021

The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses in C. elegans

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-{beta} superfamily pathway. While the role of TGF-{beta} signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-{beta} in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-{beta} in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-{beta}-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-{beta} differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-{beta} pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-{beta} signaling pathway.

immunology↗

bioRxiv2019

Feedback regulation of BMP signaling by C. elegans cuticle collagens

Cellular responsiveness to environmental cues, including changes in extracellular matrix (ECM), is critical for normal processes such as development and wound healing, but can go awry, as in oncogenesis and fibrosis. One type of molecular pathway allowing this responsiveness is the bone morphogenetic protein (BMP) signaling pathway. Due to their broad and potent functions, BMPs and their signaling pathways are highly regulated at multiple levels. In Caenorhabditis elegans, the BMP ligand DBL-1 is a major regulator of body size. We have previously shown that DBL-1/BMP signaling determines body size through transcriptional regulation of cuticle collagen genes. We have now obtained evidence of feedback regulation of DBL-1/BMP by collagen genes. We analyzed four DBL-1-regulated collagen genes that affect body size. Here we show that inactivation of any one of these cuticle collagen genes reduces DBL-1/BMP signaling, as measured by a Smad activity reporter. Furthermore, we find that depletion of these collagens reduces GFP::DBL-1 fluorescence, and acts unexpectedly at the level of dbl-1 transcription. We therefore conclude that cuticle, a type of ECM, impinges on DBL-1/BMP expression and signaling. In contrast to other characterized examples, however, the feedback regulation of DBL-1/BMP signaling by collagens is likely to be contact-independent, due to the physical separation of the cuticle from DBL-1-expressing cells in the ventral nerve cord. Our results provide an entry point into a novel mechanism of regulation of BMP signaling, with broader implications for mechanical regulation of gene expression in general.

developmental biology↗