bioRxiv Science⌕ Search

bioRxiv · 10.1101/2021.12.06.471357

Tissue-specific inhibition of protein sumoylation uncovers diverse SUMO functions during C. elegans vulval development

Abstract

The sumoylation (SUMO) pathway is involved in a variety of processes during C. elegans development, such as gonadal and vulval fate specification, cell cycle progression and maintenance of chromosome structure. The ubiquitous expression of the sumoylation machinery and its involvement in many essential processes has made it difficult to dissect the tissue-specific roles of protein sumoylation and identify the specific target proteins. To overcome these challenges, we have established tools to block protein sumoylation and degrade sumoylated target proteins in a tissue-specific and temporally controlled manner. We employed the auxin-inducible protein degradation system (AID) to down-regulate AID-tagged SUMO E3 ligase GEI-17 or the SUMO ortholog SMO-1, either in the vulval precursor cells (VPCs) or in the gonadal anchor cell (AC). Tissue-specific inhibition of GEI-17 and SMO-1 revealed diverse roles of the SUMO pathway during vulval development, such as AC positioning, basement membrane (BM) breaching, vulval cell fate specification and epithelial morphogenesis. Inhibition of sumoylation in the VPCs resulted in an abnormal shape of the vulval toroids and ectopic cell fusions. Sumoylation of the ETS transcription factor LIN-1 at K169 mediates a subset of these SUMO functions, especially the proper contraction of the ventral vulA toroids. Thus, the SUMO pathway plays diverse roles throughout vulval development.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Fergin, A., Boesch, G., Greter, N., Berger, S., Hajnal, A.. 2021-12-07. Tissue-specific inhibition of protein sumoylation uncovers diverse SUMO functions during C. elegans vulval development. https://doi.org/10.1101/2021.12.06.471357

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Alveolar and airway progenitors converge on an epigenetically encoded profibrotic state

During organ regeneration, epithelial transitional states arise from progenitors and instruct the mesenchyme to remodel the extracellular matrix. However, the identity of the progenitors, the mechanisms underlying this transition, and why these states persist in tissue fibrosis often remain elusive. Here, using lineage tracing in mice, we show that the profibrotic KRT5-/KRT17+ state in pulmonary fibrosis arises convergently from alveolar type (AT) 2 and airway secretory cells. AT1 cells generate neither KRT5-/KRT17+ nor AT2 cells. TGF-{beta}/SMAD3 acts through KMT2A and p300 to epigenetically reprogram human AT2 cells into the KRT5-/KRT17+ state. In human pulmonary fibrosis, KRT5-/KRT17+ cells slough off, and transitional cells re-epithelialize the denuded basement membrane. Transcriptionally convergent states arise in injured kidney, skin, and intestine. This work reframes fibrogenesis as the accumulation of a conserved profibrotic transitional state via ongoing turnover, not persistence alone, and nominates the state transition and its epigenetic regulators as therapeutic targets.

developmental biology↗

Dynamic mechanical sorting biases niche occupancy and lineage outcome during development of bilayered glandular epithelia

Tissue compartmentalization into basal and luminal domains is a hallmark of glandular epithelia, yet how fate boundaries are established and stabilized during dynamic morphogenesis remains a major unresolved question. Here, using mouse embryonic explants, organoids, quantitative live imaging and genetic perturbations, we show that basal-luminal compartmentalization is not maintained by fixed boundaries, but through continuous positional corrections. We show that differences in cellular adhesion and actomyosin contractility drive these positional corrections by promoting active cell sorting. We further find that these mechanical differences influence lineage specification by controlling cell positioning rather than directly instructing cell fate. Before commitment, mosaic, but not uniform, perturbation of cell mechanics alters niche occupancy and biases lineage outcome, indicating that relative mechanical properties determine access to fate-instructive niches. Conversely, perturbation of Notch and YAP remodels compartment-specific mechanical properties and cell-positioning dynamics, revealing a reciprocal coupling between lineage state and mechanical sorting. Conservation of this mechanism across four glandular epithelia of distinct origins and functions identifies dynamic mechanical sorting as a general strategy for maintaining robust tissue compartmentalization during the extensive growth and cellular rearrangements of branching morphogenesis.

developmental biology↗

Unbiased lineage tracing across the adipose organ decouples developmental origin from anatomical and transcriptomic identities

The developmental origins of individual adipose depots and whether embryonic lineage dictates adult function remain unresolved. Here, we apply in utero CRISPR-mediated barcoding lineage tracing to construct the first unbiased clonal map of adipose organ development in mice. The developmental hierarchy we uncover challenges several conventions. Remarkably, interscapular brown fat, used as the prototypical brown fat, is the most developmentally isolated brown fat; depots sharing Myf5/Pax3 lineage markers fail to cluster together; mesenteric white fat shares unexpected high clonal ancestry with brown fats despite a radically divergent transcriptome; and subcutaneous white adipose tissues converge transcriptomically despite distant developmental origins. These findings call for a reinterpretation of single-marker lineage tracing data across the adipose organ and propose that adipose depot identity is not solely encoded by embryonic lineage but is substantially shaped by the anatomical niche.

developmental biology↗