Biology subjects

Beuchle, D.

Publications and source records attributed to Beuchle, D..

4 recordsLinked to original sources

bioRxiv2026

The MAPK phosphatase VHP-1 buffers pharynx-to-body proportions against tissue-specific growth imbalance in C. elegans

Maintaining appropriate organ size ratios in the face of growth fluctuations is critical for the development of a reproducible body plan. Yet the mechanisms involved remain poorly understood. Here, we investigated how pharynx-to-body proportions are maintained in Caenorhabditis elegans, combining tissue-specific perturbations, genetic screening, and longitudinal live imaging. A genome-wide RNAi screen revealed that knock-down of the dual-specificity MAPK phosphatase VHP-1 turns animals hypersensitive to inter-tissue growth imbalance caused by pharyngeal or epidermal depletion of the mTORC1 activator RAGA-1 or the ribosomal protein RPL-22. In contrast, vhp-1 mutants tolerated global raga-1 loss, indicating a specific requirement for vhp-1 under tissue growth imbalance. Knock-down of the p38 pathway suppressed the imbalance-specific defects of vhp-1 mutants. In contrast, JNK knock-down effectively rescued the pleiotropic phenotypes of vhp-1 mutants but only weakly reduced their sensitivity to RAGA-1 imbalance, indicating that these two stress-MAPK pathways make distinct contributions to the response to growth imbalance. Finally, whole-animal VHP-1 levels increased upon epidermal RAGA-1 depletion, and epidermal VHP-1 depletion did not reproduce the sensitivity caused by global vhp-1 loss, consistent with a contribution from VHP-1 outside the growth-perturbed epidermis in buffering against local growth imbalance.

developmental biology↗

bioRxiv2025

Imp, a key regulator of transposable elements, cell growth, and differentiation genes during embryogenesis

Imps are a highly conserved family of RNA-binding proteins involved in embryonic development, cancer progression, and neurogenesis. However, the molecular pathways and RNAs regulated by Imp to control these processes remain poorly understood. Embryos derived from Imp mutant germline clones arrest development, and transcriptome analysis revealed significant dysregulation of genes involved in cell growth, differentiation, tube morphogenesis, neuronal projection development, and RNA metabolism, along with de-repression of transposable element (TE) RNAs. Consistent with these findings, Imp mutant embryos display TE-overexpression phenotypes, are smaller in size, and exhibit defective organ development, including impaired tracheal branching and gastrulation. Reduced levels of Imp at the larval neuromuscular junction (NMJ) impair synaptic bouton formation and decrease adult longevity. RIP-seq experiments showed that Imp-associated RNAs are enriched for TE RNAs. Proteomic analyses confirmed that several TE-encoded proteins are upregulated in Imp mutant embryos. Specifically, the Ty1 family retrotransposon Copia was derepressed. Consistent with recent findings that Copia is a potent inhibitor of synaptogenesis, its upregulation likely contributes to the impaired NMJ formation and broader embryonic defects observed in Imp mutants. Moreover, Imp associates with piRNA pathway proteins, ensures Piwi nuclear localization, and--like piwi mutants--its loss disrupts TE silencing and causes position-effect variegation (PEV) defects. The analysis of Imp complexes further points to potential mechanisms by which Imp may regulate TE expression. Overall, these results indicate that Imp maintains genome stability and ensures proper developmental progression and neuronal activity by regulating post-transcriptional processes and suppressing transposons.

developmental biology↗

bioRxiv2022

Differential modifications of the C-terminal tails of α-tubulin isoforms and their in vivo importance for kinesin function in Drosophila

Microtubules (MTs) are built from -/{beta}-tubulin dimers and used as tracks by kinesin and dynein motors to transport a variety of cargos, such as mRNAs, proteins, and organelles, within the cell. Tubulins are subjected to several post-translational modifications (PTMs). Glutamylation is one of them, and it is responsible for adding one or more glutamic acid residues as branched peptide chains to the C-terminal tails of both - and {beta}-tubulin. However, very little is known about the specific modifications found on the different tubulin isotypes in vivo and the role of these PTMs in MT transport and other cellular processes in vivo. In this study, we found that in Drosophila ovaries, glutamylation of -tubulin isotypes occurred clearly on the C-terminal ends of Tub84B and Tub84D (Tub84B/D). In contrast, the ovarian -tubulin, Tub67C, is not glutamylated. The C-terminal ends of Tub84B/D are glutamylated at several glutamyl side chains in various combinations. Drosophila TTLL5 is required for the mono- and poly-glutamylation of ovarian Tub84B/D and with this for the proper localization of glutamylated microtubules. Similarly, proper Kinesin-1 distribution in the germline also depends on TTLL5 as well as the refining of Staufen localization and the normal fast ooplasmic streaming with its directional movement, two processes known to depend on Kinesin-1 activities. In the nervous system, the pausing of anterograde axonal transport of mitochondria is affected by an enzymatically dead mutant of TTLL5. Our results demonstrate in vivo roles of TTLL5 in differential glutamylation of -tubulins and point to the in vivo importance of -tubulin glutamylation for Kinesin-1-dependent processes. SummaryO_LI-tubulin glutamylation was established in the C-terminal domain of Drosophila Tub84B and Tub84D (Tub84B/D). Multiple glutamyl residues were pinpointed in this domain. The female germline -tubulin, Tub67C, is, however, not glutamylated. C_LIO_LITTLL5 is required for mono- and poly-glutamylation of Tub84B/D. C_LIO_LITTLL5 is required for the proper Kinesin heavy chain (Khc) distribution in the germline, and the kinesin-based refinement of Staufen localization and ooplasmic streaming during late oogenesis. C_LIO_LITTLL5 is needed for the pausing of anterograde trafficking of mitochondria in axons. C_LI

cell biology↗

bioRxiv2020

Novel roles for BicD in pronuclear fusion and meiosis II progression via localization of the CHC/TACC/Msps complex to MII spindles

Drosophila Clathrin heavy chain (Chc) is transported by the dynein/dynactin microtubule motor through its interaction with the adaptor protein Bicaudal-D (BicD). Here we show that Drosophila BicD and Chc localize to centrosomes and spindles during mitosis and to the tandem spindles during female meiosis II. Reducing the activity of BicD::GFP specifically in freshly laid eggs revealed that BicD is essential for the production of normal female meiosis II products and for pronuclear fusion. Chc interacts with BicD and D-TACC, and BicD is needed to correctly localize the microtubule-stabilizing factors D-TACC, clathrin, and Msps to the meiosis II spindles, suggesting that BicD acts by localizing these proteins. In unfertilized eggs, reduced BicD levels cause the female meiotic products to re-enter the cell cycle. As BicD is required to localize the spindle assembly checkpoint (SAC) components Mad2 and BubR1 to the female meiotic products, it appears that BicD functions to localize them to control metaphase arrest of polar bodies. Finally, Drosophila and C. elegans orthologs of BicD and tacc are also needed for pronuclear fusion.

developmental biology↗