Biology subjects

Hsiao, E.

Publications and source records attributed to Hsiao, E..

3 recordsLinked to original sources

bioRxiv2024

Vitamin B12 partially rescues embryonic cell migration defects in C. elegans ephrin mutants by improving both propionic acid breakdown and one-carbon cycle metabolic pathways

Successful cell migration followed by tissue fusion is required for organogenesis in a number of tissues, many of which are susceptible to gene-environment interactions that can result in congenital anomalies. In C. elegans embryogenesis, one such event is the closure of the ventral cleft, which must occur as the first step in morphogenesis, otherwise embryos arrest; this process depends on ephrin signaling, but no single gene mutation is fully penetrant embryonic lethal. We exposed hermaphrodites mutant for vab-1, the C. elegans ephrin receptor, to various environmental conditions and found that vitamin B12 supplementation could partially rescue the embryonic lethality of multiple alleles from 40% survival to 63% survival. Analysis of vab-1 mutant phenotypes showed that vitamin B12 reduced the frequency of ventral cleft closure failure by promoting more normal cell positions and increased migration by the precursor cells of those that adhere to close the cleft. We found that vitamin B12 partially rescued the embryonic lethality of other ephrin pathway mutants, but not mutants that have ventral cleft defects due to cell adhesion or cell fate defects. We found that rescue by vitamin B12 depends on its functions in both mitochondrial propionic acid breakdown and the one-carbon cycle, and that antioxidant treatment can also partially rescue ephrin pathway mutants. These results are distinct from the larval response to vitamin B12, which depends only on the one-carbon cycle, emphasizing the unique metabolism of embryos and particularly the metabolic needs of migrating cells. Overall, our findings highlight the C. elegans embryo a model system to investigate gene-environment interactions and developmental metabolism.

developmental biology↗

bioRxiv2024

Brain implantation of tissue-level-soft bioelectronics 1 via embryonic development

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate1,2. These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development3-9. Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

bioengineering↗

bioRxiv2023

Ketogenic diet therapy for pediatric epilepsy is associated with alterations in the human gut microbiome that confer seizure resistance in mice

The gut microbiome modulates seizure susceptibility and the anti-seizure effects of the ketogenic diet (KD) in animal models, but whether these relationships translate to KD therapies for human drug-resistant epilepsy is unclear. Herein, we find that the clinical KD shifts the function of the gut microbiome in children with refractory epilepsy. Colonizing mice with KD-associated human gut microbes confers increased resistance to 6-Hz psychomotor seizures, as compared to colonization with gut microbes from matched pre-treatment controls. Parallel analysis of human donor and mouse recipient metagenomic and metabolomic profiles identifies subsets of shared functional features that are seen in response to KD treatment in humans and preserved upon transfer to mice fed a standard diet. These include enriched representation of microbial genes and metabolites related to anaplerosis, fatty acid beta-oxidation, and amino acid metabolism. Mice colonized with KD-associated human gut microbes further exhibit altered hippocampal and frontal cortical transcriptomic profiles relative to colonized pre-treatment controls, including differential expression of genes related to ATP synthesis, glutathione metabolism, oxidative phosphorylation, and translation. Integrative co-occurrence network analysis of the metagenomic, metabolomic, and brain transcriptomic datasets identifies features that are shared between human and mouse networks, and select microbial functional pathways and metabolites that are candidate primary drivers of hippocampal expression signatures related to epilepsy. Together, these findings reveal key microbial functions and biological pathways that are altered by clinical KD therapies for pediatric refractory epilepsy and further linked to microbiome-induced alterations in brain gene expression and seizure protection in mice.

microbiology↗