Biology subjects

Jonas, E.

Publications and source records attributed to Jonas, E..

3 recordsLinked to original sources

bioRxiv2026

Dysregulation of Hippo Signaling Pathway as a Convergent Mechanism Underlying Choroid Plexus Defects in Bipolar Disorder

Bipolar disorder (BD) is a prevalent and highly heritable psychiatric condition. Developmental mechanisms are implicated but the specific molecular origins remain unclear. The choroid plexus (ChP), which regulates cerebrospinal fluid (CSF) and brain homeostasis, has been implicated in BD, but its role is poorly understood. Here, we identify aberrant expansion of ChP in human cortical (hCOs) and ChP organoids (hChPOs) derived from, and in vivo structural magnetic resonance imaging (sMRI) scans of, individuals with BD compared to healthy comparison individuals. Single-cell transcriptomics revealed a lineage bias toward ChP fate in BD hCOs, accompanied by structural enlargement observed in both BD hChPOs and ChP in sMRI scans from individuals with BD. Comprehensive transcriptomic profiling implicates early hyperactivation of the Hippo signaling pathway in neural progenitor cells as a convergent mechanism driving ChP overgrowth. Whole-genome and genome-wide association study analyses highlight recurrent genetic variants in Hippo regulators, including STK4 and YAP1, suggesting genetic priming. BD hChPOs exhibit disrupted epithelial junctions and altered in vitro CSF secretion. These findings position the ChP as a genetically and developmentally predisposed to pathology in BD and highlight organoids as a platform for translational discovery in diagnostics and therapeutics.

developmental biology↗

bioRxiv2025

Development of a floxed Gabbr2 gene allows for widespread conditional disruption of GABBR2 and recapitulates the phenotype of germline Gabbr2 knockout mice

GABBR1 and GABBR2 are widely expressed in the brain and genetic inhibition of their function leads to widespread neurologic dysfunction and premature death in mice. Given that GABBR1 and GABBR2 heterodimerize to form a functional receptor, global knockout of GABBR1 or GABBR2 results in a similar phenotype, characterized by spontaneous epileptiform activity, hyperlocomotor activity, hyperalgesia, impaired memory and premature death. It is now known that both GABBR1 and GABBR2 are expressed in a variety of tissues outside the nervous system and that GABA-B receptors can heterodimerize with other class C GPCRs, including the extracellular calcium-sensing receptor (CaSR). Studies in vitro have demonstrated that interactions with GABBR1 and GABBR2 can alter CaSR signaling in human embryonic kidney cells and breast cancer cells. The neurologic consequences of global loss of function of GABBR1 or GABBR2 has made it difficult to study the effects of loss of GABBR function in other organs. While a conditional knockout for GABBR1 is available, the GABBR2 gene had not been "floxed". We have used CRISPR to insert loxP sites into the GABBR2 locus in mice. These mice are normal at baseline but when bred with mice expressing Cre-recombinase under the control of the ubiquitously expressed Actin gene promoter, they recapitulate the phenotype of global GABBR2 knockout mice. Phenotypic changes through the brain, including the cortex, hippocampus and cerebellum. Evidence of abnormal neuronal function, increase cell death, and changes in neuronal architecture are seen throughout the brain of CRISPR knockout mice. These mice should be useful tools to study cell type-specific loss of GABBR2 function in the brain and other organs.

neuroscience↗

bioRxiv2018

DeepLoco: Fast 3D Localization Microscopy Using Neural Networks

Single-molecule localization super-resolution microscopy (SMLM) techniques like STORM and PALM have transformed cellular microscopy by substantially increasing spatial resolution. In this paper we introduce a new algorithm for a critical part of the SMLM process: estimating the number and locations of the fluorophores in a single frame. Our algorithm can analyze a 20000-frame experimental 3D SMLM dataset in about one second -- substantially faster than real-time and existing algorithms. Our approach is straightforward but very different from existing algorithms: we train a neural network to minimize the Bayes risk under a generative model for single SMLM frames. The neural network maps a frame directly to a collection of fluorophore locations, which we compare to the ground truth using a novel loss function. While training the neural network takes several hours, it only has to be done once for a given experimental setup. After training, localizing fluorophores in new images is extremely fast -- orders of magnitude faster than existing algorithms. Faster recovery opens the door to real-time calibration and accelerated acquisition, and future work could tackle more complicated optical systems and more realistic simulators.

biophysics↗