Biology subjects

Li, E. H.

Publications and source records attributed to Li, E. H..

4 recordsLinked to original sources

bioRxiv2026

Znf804a is a regulator of circadian behaviors in zebrafish

Sleep disturbances are common among individuals with schizophrenia and can exacerbate disruptions in cognitive processes like learning and memory. Elucidating pharmacologically targetable molecular pathways perturbed by schizophrenia genes may uncover new treatment avenues. Here, we investigated the relationship of the schizophrenia-associated gene znf804a with sleep and circadian pathways. Using multi-day behavior tracking, we showed that znf804a zebrafish mutants displayed changes in sleep and circadian behaviors when light cues were removed. Through bulk RNA sequencing of fish raised under normal light cycling and dark-only conditions, we identified altered gene expression in the core and auxiliary pathways controlling circadian rhythms. Expression of fbxl3a, which encodes a modulator of the core negative feedback regulator of the clock, decreased in a dose-dependent manner as znf804a mutant copy number increased. Further analysis also revealed shifts in the relative abundance of specific transcripts, including idh1, suggesting znf804a could influence transcript processing or stability. Together, these findings link a ZNF804A ortholog to sleep and circadian behaviors and identify the regulation of fbxl3a and transcript processing as candidate mechanisms through which this schizophrenia risk gene may influence circadian biology.

genetics↗

bioRxiv2026

Diel remodeling and cellular integration of the nitroplast

Nitrogen-fixing eukaryotes were not believed to exist in nature until the recent discovery of a N2-fixing organelle, or nitroplast, in the marine microalga Braarudosphaera bigelowii. This nitroplast (formerly known as UCYN-A2) has long been recognized as key cyanobacterial contributor to global oceanic N2 fixation. However, how this novel organelle is integrated and regulated within the architecture of a eukaryotic cell remains unclear. Here, we combine multiscale volumetric imaging with cryo-electron tomography to resolve the native architecture, cellular integration, and diel remodeling of the nitroplast in cultured and environmental cells. We find that the nitroplast occupies up to 10% of the cell volume and exhibits close interfaces with multiple host organelles through membrane contact sites, while integration of this metabolically demanding compartment does not disrupt global scaling of host organelles. Interestingly, the chloroplast-to-nitroplast volume ratio is conserved across distinct life stages. Cryo-electron tomography reveals that the nitroplast retains a reinforced four-layer cyanobacterial envelope and is additionally surrounded by two host-derived layers that remodel across the day-night cycle. During daytime N2 fixation, these host-derived barriers become locally discontinuous and the organelle interface becomes enriched with two distinct vesicle populations. Our findings suggest that dynamic control of organelle accessibility through transient membrane gating represents a fundamental strategy by which eukaryotic cells could domesticate new endosymbiotic functions during early organellogenesis.

cell biology↗

bioRxiv2021

Inositol Polyphosphate-5-phosphatase K (Inpp5k) enhances sprouting of corticospinal tract axons after CNS trauma.

Failure of CNS neurons to mount a significant intrinsic growth response after trauma results in chronic functional deficits after spinal cord injury. Approaches to identify novel axon growth activators include transcriptional and repressor screening of embryonic cortical and retinal ganglion neurons in vitro. These high throughput approaches have identified several candidates; however, their inability to comprehensively model the adult CNS has resulted in their exploitation in vivo failing to stimulate significant anatomical and functional gains. To identify novel cell autonomous axon growth activators while maintaining CNS complexity, we screened intact adult corticospinal neurons (CSNs) undergoing functional plasticity after unilateral pyramidotomy. RNA-seq of intact sprouting corticospinal tract (CST) axons showed an enrichment of genes in the 3-phosphoinositide degradation pathways, including six 5-phosphatases. We explored whether Inositol Polyphosphate-5-phosphatase K (Inpp5k) could enhance CST axon growth in clinical models of CNS trauma. Overexpression of Inpp5k in intact adult CSNs enhanced sprouting of intact CST terminals into the denervated cervical cord after pyramidotomy and cortical stroke lesion. Inpp5k overexpression also stimulated sprouting of CST axons in the cervical cord after acute and chronic severe thoracic spinal contusion. We show that Inpp5k stimulates axon growth by elevating the density of active cofilin in the cytosol of labile growth cones, thus stimulating actin polymerization and enhancing microtubule protrusion into distal filopodia. This study identifies Inpp5k as a novel CST growth activator and underscores the veracity of using in vivo transcriptional screening to identify the next generation of cell autonomous factors capable of repairing the damaged CNS. SIGNIFICANCE STATEMENTNeurological recovery is limited after spinal cord injury as CNS neurons are incapable of self-repair post trauma. In vitro screening strategies exploit the intrinsically high growth capacity of embryonic CNS neurons to identify novel axon growth activators. While promising candidates have been shown to stimulate axon growth in vivo, concomitant functional recovery remains incomplete. Using transcriptional profiling of intact adult corticospinal tract neurons undergoing functional plasticity, we identified Inpp5k as a novel axon growth activator capable of stimulating CST axon growth after pyramidotomy, stroke and acute and chronic contusion injuries. These data support using in vivo screening approaches to identify novel axon growth activators.

neuroscience↗

bioRxiv2018

Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions

Genomic studies have identified hundreds of candidate genes near loci associated with risk for schizophrenia. To define candidates and their functions, we mutated zebrafish orthologues of 132 human schizophrenia-associated genes and created a phenotype atlas consisting of whole-brain activity maps, brain structural differences, and profiles of behavioral abnormalities. Phenotypes were diverse but specific, including altered forebrain development and decreased prepulse inhibition. Exploration of these datasets identified promising candidates in more than 10 gene-rich regions, including the magnesium transporter cnnm2 and the translational repressor gigyf2, and revealed shared anatomical sites of activity differences, including the pallium, hypothalamus or tectum. Single-cell RNA sequencing uncovered an essential role for the understudied transcription factor znf536 in the development of forebrain neurons implicated in social behavior and stress. This phenotypic landscape of schizophrenia-associated genes prioritizes more than 30 candidates for further study and provides hypotheses to bridge the divide between genetic association and biological mechanism.

genetics↗