Biology subjects

Hoyer, J.

Publications and source records attributed to Hoyer, J..

6 recordsLinked to original sources

bioRxiv2025

Mechanics regulate the postembryonic developmental maturation and function of sensory neurons in a pre-vertebrate chordate.

Physical forces are emerging as important contributors to a wide diversity of biological processes across multiple scales and contexts. The development of the nervous system is infuenced by mechanical forces exerted on neurons and glia by the surrounding environment. However, the extent to which tissue mechanics influence the function and morphology of the post-embryonic nervous system remains unclear. Here we leverage the post-embryonic larval period of the pre-vertebrate chordate Ciona intestinalis to study the dynamic interplay between nervous system mechanics, cellular and nuclear morphology and neuronal function. During this post-embryonic period the larval head undergoes substantial stretching along the anterior-posterior axis. We show that this macroscopic morphological change is associated with a significant change in cell and nuclear shape (stretching) of the polymodal sensory neurons located in the papillar organs. Using FRET based genetically encoded tension sensors we show that mechanical tension at the focal adhesions and the nuclear envelope of these papillar sensory neurons increases with time. At the functional level Ca2+ imaging experiments reveal that presentation and removal of a chemosensory stimulus that promotes settlement and metamorphosis elicits significantly stronger responses in late swimming larvae papillar neurons compared to those newly hatched ones. Finally, by combining optoGEF-RhoA dependent control of cellular forces and Ca2+ imaging we demonstrate that the strength of chemosensory responses and settlement behavior can be modulated by mechanical forces.

developmental biology↗

bioRxiv2024

Anoctamins mediate polymodal sensory perception and larval metamorphosis in a non-vertebrate chordate.

An exceptional feature of most animals is their ability to perceive diverse sensory cues from the environment and integrate this information in their brain to yield ethologically relevant behavioral output. For the myriad of marine species, the ocean represents a complex sensory environment, which acts as a crucible of evolution for polymodal sensory perception. The cellular and molecular bases of polymodal sensory perception in a marine environment remain enigmatic. Here we use Ca2+ imaging and quantitative behavioral analysis to show that in the tunicate Ciona intestinalis two members of the evolutionarily conserved Anoctamin family1-4 (Tmem16E/Ano5 and Tmem16F/Ano6), are required for sensing chemosensory and mechanosensory metamorphic cues. We find that they act by modulating neuronal excitability and Ca2+ response kinetics in the primary sensory neurons and axial columnar cells of the papillae, a widely conserved sensory-adhesive organ across ascidians5-9. Finally, we use electrophysiological recordings and a scramblase assay in tissue culture to demonstrate that Tmem16E/Ano5 acts as a channel, while Tmem16F/Ano6 is a bifunctional ion channel and phospholipid scramblase. Our results establish Ano5 and Ano6 as novel players in the zooplanktonic, pre-vertebrate molecular toolkit that controls polymodal sensory perception in aquatic environments.

neuroscience↗

bioRxiv2023

Polymodal sensory perception of mechanical and chemical cues drives robust settlement and metamorphosis of a marine pre-vertebrate zooplanktonic larva.

The Earths oceans brim with an incredible diversity of microscopic planktonic animals, many of which correspond to the transient larval stage in the life cycles of benthic marine organisms. The mechanisms by which marine larvae use their nervous system to sense and process diverse environmental cues (physical and chemical) in the water column and the benthos to settle and metamorphose is a major problem across the fields of neuroscience, development, evolution and ecology, yet they remain largely unclear. Here, we employ Ca2+ imaging and behavioral assays using the larval form of the protochordate Ciona intestinalis to characterise the mechanical and chemical stimuli these larvae respond to during settlement and metamorphosis. We also identify the polymodal sensory cells that detect these stimuli. Whole brain Ca2+ imaging further revealed that the presentation or removal of ethological chemosensory stimuli engages the activities of different neuronal sub-populations resulting in brain state changes, which may underlie behavioral action selections and metamorphosis. Finally, chemogenetic interrogation coupled to behavioral analysis reveals that peptidergic sensory neurons including polymodal cells capable of chemotactile perception and chemosensory/neurosecretory cells of proto-placodal ectoderm origin play a pivotal role in regulating stimulus induced settlement and metamorphosis. This work suggests that marine zooplanktonic larvae utilise their streamlined nervous systems to perform multimodal integration of ethologically physical and chemical cues to explore the oceanic water column and benthos.

neuroscience↗

bioRxiv2020

Mapping calcium dynamics in a developing tubular structure.

Calcium is a ubiquitous and versatile second messenger that plays a central role in the development and function of a wide range of cell types, tissues and organs. Despite significant recent progress in the understanding of calcium (Ca2+) signalling in organs such as the developing and adult brain, we have relatively little knowledge of the contribution of Ca2+ to the development of tubes, structures widely present in multicellular organisms. Here we image Ca2+ dynamics in the developing notochord of Ciona intestinalis. We show that notochord cells exhibit distinct Ca2+ dynamics during specific morphogenetic events such as cell intercalation, cell elongation and tubulogenesis. We used an optogenetically controlled Ca2+ actuator to show that sequestration of Ca2+ results in defective notochord cell intercalation, and pharmacological inhibition to reveal that stretch-activated ion channels (SACs), inositol triphosphate receptor (IP3R) signalling, Store Operated Calcium Entry (SOCE), Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and gap junctions are required for regulating notochord Ca2+ activity during tubulogenesis. Cytoskeletal rearrangements drive the cell shape changes that accompany tubulogenesis. In line with this, we show that Ca2+ signalling modulates reorganization of the cytoskeletal network across the morphogenetic events leading up to and during tubulogenesis of the notochord. We additionally demonstrate that perturbation of the actin cytoskeleton drastically remodels Ca2+ dynamics, suggesting a feedback mechanism between actin dynamics and Ca2+ signalling during notochord development. This work provides a framework to quantitatively define how Ca2+ signalling regulates tubulogenesis using the notochord as model organ, a defining structure of all chordates.

developmental biology↗

bioRxiv2019

Panel Sequencing in Uterine Leiomyomas identifies Missense Mutations associated with immunohistochemical Fumarate Hydratase (FH)-Loss

ABSTRACTUterine leiomyomas (ULs) constitute a considerable health burden in the general female population. The fumarate hydratase (FH) deficient subtype is found in up to 1.6% and can occur in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.We sequenced 13 FH deficient ULs from a previous immunohistochemical screen using a targeted panel and identified biallelic FH variants in all. In eight, we found a FH point mutation (two truncating, six missense) with evidence for loss of the second allele. Variant allele-frequencies in all cases with a point mutation pointed to somatic variants. Spatial clustering of the identified missense variants in the lyase domain indicated altered fumarase oligomerization with subsequent degradation as explanation for the observed FH deficiency. Biallelic FH deletions in five tumors confirm the importance of copy number loss as mutational mechanism.By curating all pathogenic FH variants and calculating their population frequency, we estimate a carrier frequency of up to 1/2,563. Comparing with the prevalence of FH deficient ULs, we conclude that most are sporadic and estimate 2.7 - 13.9% of females with an FH deficient UL to carry a germline FH variant.Further prospective tumor/normal sequencing studies are needed to develop a reliable screening strategy for HLRCC in women with ULs.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

bioRxiv2019

Prenatal diagnosis of HNF1B-associated renal cysts: Need to differentiate intragenic variants from 17q12 microdeletion syndrome?

ObjectiveLarge deletions of chromosome 17q12 (17q12DS) or intragenic variants in HNF1B are associated with variable developmental, endocrine and renal anomalies, often already noted prenatally as hyperechogenic/cystic kidneys. Here, we describe pre- and postnatal phenotypes of seven individuals with HNF1B aberrations and compare their clinical and genetic data to previous studies.\n\nMethodsPrenatal sequencing and postnatal chromosomal microarray analysis was performed in seven individuals with renal and/or neurodevelopmental phenotypes. We evaluated HNF1B-related clinical features from 82 studies and reclassified 192 reported intragenic HNF1B variants.\n\nResultsIn a prenatal case, we identified a novel in-frame deletion p.(Gly239del) within the HNF1B DNA binding domain, a mutational hotspot as demonstrated by spatial clustering analysis and high computational prediction scores. The six postnatally diagnosed individuals harbored 17q12 microdeletions of varying size. Literature screening revealed highly variable reporting of HNF1B-associated clinical traits. Overall, developmental delay was more frequent in 17q12DS carriers, although both mutation groups showed a high phenotypic heterogeneity. The reclassification of all previously reported intragenic HNF1B variants provided an up-to-date overview of the mutational spectrum.\n\nConclusionsWe highlight the value of prenatal HNF1B screening in renal developmental diseases. Standardized clinical reporting and systematic classification of HNF1B variants is necessary for a more accurate risk quantification of pre- and postnatal clinical features, improving genetic counseling and prenatal decision-making.

genetics↗