Biology subjects

Schumann, I.

Publications and source records attributed to Schumann, I..

4 recordsLinked to original sources

bioRxiv2023

Drosophila Bchs overexpression recapitulates human WDFY3 neurodevelopmental phenotypes with implications for glial cell involvement in altered head circumference

The autophagy adaptor WDFY3 is linked to neurodevelopmental delay and altered brain size. Loss-of-function variants are associated with an increased brain size in both humans and mice. We thus, hypothesized that the microcephaly observed in some of the patients may be related to a gain-of-function of the WDFY3 gene product. While the role of WDFY3 loss-of-function has been studied extensively in neurons, little is known about the effects of WDFY3 overexpression in different neural cell types. We utilized a Drosophila melanogaster overexpression model to investigate the effect of the WDFY3 ortholog Bchs (blue cheese) on development, CNS size, and gene expression profiles. Glial and neuronal overexpression of Bchs impaired CNS development, locomotion and autophagy. Glial overexpression of Bchs also altered CNS size significantly. We identified 79 genes that were differentially expressed and overlapped in flies that overexpress Bchs in glial and neuronal cells, respectively. Additionally, upon neuronal Bchs overexpression differentially expressed genes clustered in gene ontology categories associated with autophagy and mitochondria. Our data indicate that WDFY3/Bchs overexpression in both neurons and glial cells results in impaired neural development, which corresponds to symptoms observed in WDFY3-related neurodevelopmental delay.

neuroscience↗

bioRxiv2023

altAFplotter: a web app for reliable UPD detection in NGS diagnostics

The detection of uniparental disomies (the inheritance of both chromosome homologues from a single parent, UPDs) is not part of most standard or commercial NGS-pipelines in human genetics and thus a common gap in NGS diagnostics. To address this we developed a tool for UPD-detection based on panel, exome or whole genome sequencing data which is easy to use and publicly available. Detection of UPDs and delineation of different UPD types is achieved by combining two approaches: detection of runs of homozygosity and their extent per chromosome and investigation of variant inheritance and the ratios of uniparentally inherited variants per chromosome. Both metrics have been carefully tuned with a large set of positive and negative controls to allow reliable and sensitive detection of UPDs. We provide a web tool that can be easily accessed and used to enable geneticists to perform a sensitive UPD-detection analysis based on exome, panel and whole genome sequencing data (.vcf-files) on the fly.

bioinformatics↗

bioRxiv2021

Ethanol-guided behavior in Drosophila larvae

Chemosensory signals allow vertebrates and invertebrates not only to orient in its environment toward energy-rich food sources to maintain nutrition but also to avoid unpleasant or even poisonous substrates. Ethanol is a substance found in the natural environment of Drosophila melanogaster. Accordingly, D. melanogaster has evolved specific sensory systems, physiological adaptations, and associated behaviors at its larval and adult stage to perceive and process ethanol. To systematically analyze how D. melanogaster larvae respond to naturally occurring ethanol, we examined ethanol-induced behavior in great detail by parametrically reevaluating existing approaches and comparing them with new experiments. Using behavioral assays, we confirm that larvae are attracted to different concentrations of ethanol in their environment. This behavior is controlled both by olfactory and contact cues. It is independent of previous exposure to ethanol in their food. Moreover, moderate, naturally occurring ethanol concentration of 4% results in increased larval fitness. On the contrary, higher concentrations of 10% and 20% ethanol, which rarely or never appear in nature, increase larval mortality. Finally, ethanol also serves as a positive teaching signal in learning and memory and updates valence associated with simultaneously processed odor information. Since information on how larvae perceive and process ethanol at the genetic and neuronal level is limited, the establishment of standardized assays described here is an important step towards their discovery.

animal behavior and cognition↗

bioRxiv2020

The PEDtracker: an automatic staging approach for Drosophila melanogaster larvae

The post-embryonal development of arthropod species, including crustaceans and insects, is characterized by ecdysis or molting. This process defines growth stages and is controlled by a conserved neuroendocrine system. Each molting event is divided in several critical time points, such as pre-molt, molt and post-molt, and leaves the animals in a temporarily highly vulnerable state while their cuticle is re-hardening. The molting events occur in an immediate ecdysis sequence within a specific time window during the development. Each sub-stage takes only a short amount of time, which is generally in the order of minutes. To find these relatively short behavioral events, one needs to follow the entire post-embryonal development over several days. As the manual detection of the ecdysis sequence is time consuming and error prone, we designed a monitoring system to facilitate the continuous observation of the post-embryonal development of the fruit fly Drosophila melanogaster. Under constant environmental conditions we are able to observe the life cycle from the embryonic state to the adult, which takes about ten days in this species. Specific processing algorithms developed and implemented in Fiji and R allow us to determine unique behavioral events on an individual level - including egg hatching, ecdysis and pupation. In addition, we measured growth rates and activity patterns for individual larvae. Our newly created RPackage PEDtracker can predict critical developmental events and thus offers the possibility to perform automated screens that identify changes in various aspects of larval development. In conclusion, the PEDtracker system presented in this study represents the basis for automated real-time staging and analysis not only for the arthropod development.

animal behavior and cognition↗