Biology subjects

Cox, C. L.

Publications and source records attributed to Cox, C. L..

4 recordsLinked to original sources

bioRxiv2025

Widespread male-female expression imbalance of X-linked genes across phrynosomatid lizards

Classic theory on sex chromosome evolution predicts that selection should restore ancestral diploid expression for hemizygous X-linked genes in males. However, this dosage compensation is often incomplete, leaving X enriched for genes with female-biased expression. In this context, iguanian lizards are noteworthy among vertebrates because several species from separate families appear to exhibit both near-complete dosage compensation and male-female expression balance across their ancient, homologous X chromosomes. We tested for this pattern in a phrynosomatid iguanian, Sceloporus undulatus (Eastern Fence Lizard), and instead found that both ancient and more recently sex-linked regions of the X chromosome are enriched for genes with female-biased expression, regardless of age (neonate, maturing, adult) or tissue (brain, liver, muscle). By expanding our analysis across 10 phrynosomatid species spanning 4 genera, we found that male-female expression imbalance on the ancestral region of X is phylogenetically conserved. We also found that an inferred chromosomal rearrangement in the S. jarrovii lineage has resulted in the novel acquisition of female-biased expression by a formerly autosomal region. Whereas sex-biased expression of the ancestral region of X is primarily due to females overexpressing X-linked genes relative to autosomal genes, sex-biased expression of these formerly autosomal genes in S. jarrovii is primarily due to males underexpressing this putative neo-X region. We conclude that male-female expression imbalance on X is widespread across phrynosomatids, potentially reflecting both overexpression in females for ancestral regions that have evolved dosage compensation and underexpression in males for neo-X regions in which dosage compensation has yet to evolve.

evolutionary biology↗

bioRxiv2022

Heterogeneity of burst firing in mouse thalamic reticular nucleus neurons

The thalamic reticular nucleus (TRN) sits at the interface of the thalamus and neocortex and provides the majority of inhibition to thalamic relay nuclei. Functionally, the activity of TRN neurons can impact sensory processing and may influence arousal states. TRN neurons discharge action potentials in two distinct output modes: tonic or burst firing. Burst output, a transient high frequency discharge of action potentials, is dependent on the activation of transient low-threshold voltage-dependent T-type calcium current (IT). In our current study, we identify a broad range of burst firing frequencies in TRN neurons, which depend on the activation of IT. The amplitude of the low-threshold calcium spike (LTS) underlying the burst positively correlated with burst frequency and number of action potentials per burst. Activation of small conductance calcium-activated potassium (SK) channels on TRN neurons can impact burst discharge. Attenuation of SK channels increased TRN neuron burst frequency through an increase in LTS duration, but not magnitude. The broad range of burst firing frequencies could provide distinct downstream inhibition within thalamic nuclei.

neuroscience↗

bioRxiv2022

Structural and functional changes of pyramidal neurons at the site of an implanted microelectrode array in rat primary motor cortex

Devices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the initial surgical insertion and subsequent tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 m-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disruption of the dendritic arbor of neurons near (<100 m) the device surface at both time points, as well as a significant reduction in spine densities. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents (sEPSCs), a loss in sag amplitude, and an increase in spike frequency adaptation at the 6 week time point. Interestingly, we also noted a significant increase in filopodial density in neurons surrounding devices. Results were similar for polyimide and silicon-based electrodes. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes.

bioengineering↗

bioRxiv2020

A chromosome-level genome assembly for the Eastern Fence Lizard (Sceloporus undulatus), a reptile model for physiological and evolutionary ecology

High-quality genomic resources facilitate population-level and species-level comparisons to answer questions about behavioral ecology, morphological and physiological adaptations, as well as the evolution of genomic architecture. Squamate reptiles (lizards and snakes) are particularly diverse in characteristics that have intrigued evolutionary biologists, but high-quality genomic resources for squamates are relatively sparse. Lizards in the genus Sceloporus have a long history as important ecological, evolutionary, and physiological models, making them a valuable target for the development of genomic resources. We present a high-quality chromosome-level reference genome assembly, SceUnd1.0, (utilizing 10X Genomics Chromium, HiC, and PacBio data) and tissue/developmental stage transcriptomes for the Eastern Fence Lizard, Sceloporus undulatus. We performed synteny analysis with other available squamate chromosome-level assemblies to identify broad patterns of chromosome evolution including the fusion of micro- and macrochromosomes in S. undulatus. Using this new S. undulatus genome assembly we conducted reference-based assemblies for 34 other Sceloporus species to improve draft nuclear genomes assemblies from 1% coverage to 43% coverage on average. Across these species, typically >90% of reads mapped for species within 20 million years divergence from S. undulatus, this dropped to 75% reads mapped for species at 35 million years divergence. Finally we use RNAseq and whole genome resequencing data to compare the three assemblies as references, each representing an increased level of sequencing, cost and assembly efforts: Supernova Assembly with data from10X Genomics Chromium library; HiRise Assembly that added data from HiC library; and PBJelly Assembly that added data from PacBio sequencing. We found that the Supernova Assembly contained the full genome and was a suitable reference for RNAseq, but the chromosome-level scaffolds provided by the addition of the HiC data allowed the reference to be used for other whole genome analysis, including synteny and whole genome association mapping analyses. The addition of PacBio data provided negligible gains. Overall, these new genomic resources provide valuable tools for advanced molecular analysis of an organism that has become a model in physiology and evolutionary ecology.

genomics↗