Biology subjects

Baumgartner, S.

Publications and source records attributed to Baumgartner, S..

6 recordsLinked to original sources

bioRxiv2024

The choroid plexus maintains ventricle volume and adult subventricular zone neuroblast pool, which facilitates post-stroke neurogenesis

The brains neuroreparative capacity after injuries such as ischemic stroke is contained in the brains neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here we report a mouse genetic tool (the ROSA26iDTR mouse line) for non-invasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at one-month post-ablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the MCAo model of ischemic stroke, neuroblast migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important and novel role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke.

neuroscience↗

bioRxiv2023

Revisiting bicoid function: complete inactivation reveals an additional fundamental role in Drosophila egg geometry specification.

IntroductionThe bicoid (bcd) gene in Drosophila has served as a paradigm for a morphogen in textbooks for decades. Discovered in 1986 as a mutation affecting anterior development in the embryo, its expression pattern as a protein gradient later confirmed the prediction from transplantation experiments. These experiments suggested that the protein fulfills the criteria of a true morphogen, with the existence of a homeodomain crucial for activation of genes along the anterior-posterior axis, based on the concentration of the morphogen. The bcd gene undergoes alternative splicing, resulting in, among other isoforms, a small and often neglected isoform with low abundance, which lacks the homeodomain, termed small bicoid (smbcd). Most importantly, all known classical strong bcd alleles used in the past to determine bcd function apparently do not affect the function of this isoform. ResultsTo overcome the uncertainty regarding which isoform regulates what, I removed the bcd locus entirely using CRISPR technology. bcdCRISPR eggs exhibited a short and round appearance. The phenotype could be ascribed to smbcd because all bcd alleles affecting the function of the major transcript, termed large bicoid (lgbcd) showed normally sized eggs. Several patterning genes for the embryo showed expression in the oocyte, and their expression patterns were altered in bcdCRISPR oocytes. In bcdCRISPR embryos, all downstream segmentation genes showed altered expression patterns, consistent with the expression patterns in "classical" alleles; however, due to the altered egg geometry resulting in fewer blastoderm nuclei, additional constraints came into play, further affecting their expression patterns. ConclusionsThis study unveils a novel and fundamental role of bcd in shaping the eggs geometry. This discovery demands a comprehensive revision of our understanding of this important patterning gene and prompts a reevaluation of past experiments conducted under the assumption that bcd mutants were bcdnull-mutants.

developmental biology↗

bioRxiv2021

Anti-fibrotic activity of an antimicrobial peptide in a Drosophila model.

Fibrotic lesions accompany several pathological conditions including tumors. We show that expression of a dominant-active form of the Ras oncogene in Drosophila salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apico-basal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide Drosomycin (Drs), which also restores secretory activity of the SGs. In addition to ECM components, both Drs and F-actin localize to fibrotic lesions.

immunology↗

bioRxiv2021

Agricultural fertilization with poultry manure results in persistent environmental contamination with the pathogen Clostridioides difficile

During a field experiment applying broiler manure for fertilization of agricultural land, we detected viable Clostridioides (formerly, Clostridium) difficile in broiler feces, manure, dust, and fertilized soil. A large diversity of toxigenic C. difficile isolates was recovered, including PCR ribotypes common from human disease. Genomic relatedness of C. difficile isolates from dust and from soil, recovered more than two years after fertilization, traced their origins to the specific chicken farm that had delivered the manure. We present evidence of long-term contamination of agricultural soil with manure-derived C. difficile and demonstrate the potential for airborne dispersal of C. difficile through dust emissions during manure application. Clostridioides genome sequences virtually identical to those from manure had been recovered from chicken meat and from human infections in previous studies, suggesting broiler-associated C. difficile are capable of zoonotic transmission.

microbiology↗

bioRxiv2020

Quantification reveals early dynamics in Drosophila maternal gradients

The Bicoid (Bcd) protein is a primary determinant of early anterior-posterior (AP) axis specification in Drosophila embryogenesis. This morphogen is spatially distributed in an anterior-high gradient, and affects particular AP cell fates in a concentration-dependent manner. The early distribution and dynamics of the bicoid (bcd) mRNA, the source for the Bcd protein gradient, is not well understood, leaving a number of open questions for how Bcd positional information develops and is regulated. Confocal microscope images of whole early embryos, stained for bcd mRNA or the Staufen (Stau) protein involved in its transport, were processed to extract quantitative AP intensity profiles at two depths (apical - under the embryo surface but above the nuclear layer; and basal - below the nuclei). Each profile was quantified by a two- (or three-) exponential equation. The parameters of these equations were used to analyze the early developmental dynamics of bcd. Analysis of 1D profiles was compared with 2D intensity surfaces from the same images. This approach reveals strong early changes in bcd and Stau, which appear to be coordinated. We can unambiguously discriminate three stages in early development using the exponential parameters: pre-blastoderm, syncytial blastoderm and cellularization. Key features which differ in this period are how fast the first exponential (anterior component) of the apical profile drops with distance and whether it is higher or lower than the basal first exponential. We can further discriminate early and late embryos within the pre-blastoderm stage, depending on how quickly the anterior exponential drops. This relates to the posterior-wards spread of bcd in the first hour of development. Both bcd and Stau show several redistributions in the head cytoplasm, quite probably related to nuclear activity: first shifting inwards towards the core plasm, forming either protrusions (early pre-blastoderm) or round aggregations (early nuclear cleavage cycles, cc, 13 and 14), then moving to the embryo surface and spreading posteriorly. These movements are seen both with the 2D surface study and the 1D profile analysis. The continued spreading of bcd can be tracked from the time of nuclear layer formation (later pre-blastoderm) to the later syncytial blastoderm stages by the progressive loss of steepness of the apical anterior exponential (for both bcd and Stau). Finally, at the beginning of cc14 (cellularization stage) we see a distinctive flip from the basal anterior gradient being higher to the apical gradient being higher (for both bcd and Stau). Quantitative analysis reveals substantial (and correlated) bcd and Stau redistributions during early development, supporting that the distribution and dynamics of bcd mRNA are key factors in the formation and maintenance of the Bcd protein morphogenetic gradient. This analysis reveals the complex and dynamic nature of bcd redistribution, particularly in the head cytoplasm. These resemble observations in oogenesis; their role and significance have yet to be clarified. The observed co-localization during redistribution of bcd and Stau may indicate the involvement of active transport.

systems biology↗

bioRxiv2018

Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system plasticity

Basement membranes (BMs) are specialized layers of extracellular matrix (ECM) mainly composed of Laminin, type IV Collagen, Perlecan and Nidogen/entactin (NDG). While the essential and evolutionary conserved functions of Laminin, Collagen and Perlecan are well documented in Drosophila and other species, the proposed role of NDG as the major ECM linker molecule has been challenged by several in vivo studies revealing that NDG is dispensable for viability and BM formation. Here, we report the characterization of the single Ndg gene in Drosophila. Embryonic Ndg expression differed from that of other BM components and was primarily observed in mesodermal tissues and the chordotonal organs, whereas NDG protein localized to all BMs. While loss of Laminin strongly affected BM-localization of NDG, Ndg null mutants exhibited no overt changes in the distribution of BM core components. However, loss of NDG led to ultrastructural BM defects compromising barrier function and stability in vivo. Although Ndg mutants were viable, loss of NDG led to decreased fecundity in flies as well as impaired crawling behavior and reduced response to vibrational stimuli in larvae. Further morphological analysis revealed accompanying defects in the larval peripheral nervous system especially in the chordotonal organs and the neuromuscular junction (NMJ), where Ndg genetically interacted with the Leukocyte-antigen-related-like (Lar) receptor gene to regulate NMJ extension and synaptic differentiation. Taken together, our analysis suggests that NDG is not essential for BM assembly but mediates BM stability and ECM-dependent neural plasticity during Drosophila development.\n\nSummary StatementIn this study we characterize Drosophila Nidogen/Entactin (Ndg) mutants revealing that loss of Ndg impairs basement membrane (BM) stability and permeability as well as proper function of the nervous system.

developmental biology↗