Biology subjects

Schneuwly, S.

Publications and source records attributed to Schneuwly, S..

4 recordsLinked to original sources

bioRxiv2024

The pivotal role of Drgx in survival, wiring and identity of T4/T5 neurons

The development of Drosophila melanogasters T4/T5 motion-sensing neurons has been extensively studied. Despite identifying many genes, important developmental steps remain unknown. This study investigates the Paired-like homeobox transcription factor Dorsal root ganglia homeobox (Drgx) in T4/T5 neuron development. Drgx expression initiates in T4/T5 neuroblasts and persists in mature neurons. Knockdowns using T4/T5-specific drivers yield distinct phenotypes in the optic lobe, including dendrite mistargeting and reduced lobular plate size due to apoptosis in early knockdowns. Late knockdowns exhibit only extensive mistargeting. Therefore, Drgx plays a dual role, initially inhibiting apoptosis and later on establishing T4/T5 neuron identity and circuit formation. Targeted DamID (TaDa) and RNA-sequencing (RNA-seq) identify Drgx target genes involved in apoptosis and neuron projection development. Therefore, Drgx orchestrates vital stages in T4/T5 neuron development, influencing survival, identity, and circuitry and connects to the previously identified transcription factor Sox102F as a target of Drgx. Summary statementThe Paired-like homeobox transcription factor Drgx is essential for the correct establishment of the identity of a specific type of motion vision neurons in Drosophila.

developmental biology↗

bioRxiv2020

Disarrangement of Endoplasmic reticulum-mitochondria communication impairs Ca2+ homeostasis in FRDA

Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in gene FXN, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, an analysis of calcium management and of integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatment with antioxidants. In agreement, promoting mitochondrial calcium uptake was sufficient to restore several defects caused by frataxin deficiency in Drosophila Melanogaster. Remarkably, our findings describe for the first time frataxin as a member of the protein network of MAMs, where interacts with two of the main proteins implicated in endoplasmic reticulum-mitochondria communication. These results suggest a new role of frataxin, indicate that FRDA goes beyond mitochondrial defects and highlight MAMs as novel therapeutic candidates to improve patients conditions.

neuroscience↗

bioRxiv2020

Hedgehog Signalling Modulates Glial Proteostasis and Lifespan.

The conserved Hedgehog (Hh) signaling pathway has a well-established role in animal development, however its function during adulthood remains largely unknown. Here, we investigated whether the Hh signaling pathway is active during adult life in Drosophila melanogaster and uncovered a protective function for Hh signaling in coordinating correct proteostasis in glial cells. Adult-specific depletion of Hh reduces lifespan, locomotor activity and dopaminergic neuron integrity. Conversely, increased expression of Hh extends lifespan and improves fitness. Moreover, Hh pathway activation in glia rescues the lifespan and age-associated defects of hedgehog (hh) mutants. At the molecular level, the Hh pathway regulates downstream chaperones, principally hsp40 and hsp68, whose overexpression in glial cells rescues the shortened lifespan and proteostasis defects of hh mutants. Finally, we demonstrate the protective ability of Hh signalling in a Drosophila Alzheimers disease model expressing human Amyloid Beta (A{beta}1-42) in the glia. Overall, we propose that Hh signalling is requisite for lifespan determination and correct proteostasis in glial cells and may have potential in ameliorating a wide range of degenerative diseases.

neuroscience↗

bioRxiv2018

The Drosophila fussel gene is required for bitter gustatory neuron differentiation acting within an Rpd3 dependent chromatin modifying complex

Members of the Ski/Sno protein family are classified as proto-oncogenes and act as negative regulators of the TGF-{beta}/BMP-pathways in vertebrates and invertebrates. A newly identified member of this protein family is fussel (fuss), the Drosophila homologue of the human functional Smad suppressing elements (fussel-15 and fussel-18). We and others have shown that Fuss interacts with SMAD4 and that overexpression leads to a strong inhibition of Dpp signaling. However, to be able to characterize the endogenous Fuss function in Drosophila melanogaster, we have generated a number of state of the art tools including anti-Fuss antibodies, specific fuss-Gal4 lines and fuss mutant fly lines via the CRISPR/Cas9 system. Fuss is a predominantly nuclear, postmitotic protein, mainly expressed in interneurons and fuss mutants are fully viable without any obvious developmental phenotype. To identify potential target genes or cells affected in fuss mutants, we conducted targeted DamID experiments in adult flies, which revealed the function of fuss in bitter gustatory neurons. We fully characterized fuss expression in the adult proboscis and by using food choice assays we were able to show that fuss mutants display defects in detecting bitter compounds. This correlated with a reduction of gustatory receptor gene expression (Gr33a, Gr66a, Gr93a) providing a molecular link to the behavioral phenotype. In addition, Fuss interacts with Rpd3, and downregulation of rpd3 in gustatory neurons phenocopies the loss of Fuss expression. Surprisingly, there is no colocalization of Fuss with phosphorylated Mad in the larval central nervous system, excluding a direct involvement of Fuss in Dpp/BMP signaling.\n\nHere we provide a first and exciting link of Fuss function in gustatory bitter neurons. Although gustatory receptors have been well characterized, little is known regarding the differentiation and maturation of gustatory neurons. This work therefore reveals Fuss as a pivotal element for the proper differentiation of bitter gustatory neurons acting within a chromatin modifying complex.

developmental biology↗