Biology subjects

Frazel, P. W.

Publications and source records attributed to Frazel, P. W..

3 recordsLinked to original sources

bioRxiv2026

Ancient Somatosensory Circuit Architectures Employ Flexible Molecular Strategies

The extent to which conserved neural circuit architectures depend on shared molecular specification programs remains unclear. Here, we address this question by examining the somatosensory system of the little skate, Leucoraja erinacea, an early-diverging vertebrate that retains ancestral features of both finned and limb-based body plans. We show that core features of somatosensory circuit organization, including laminar organization of the spinal cord and dorsally restricted targeting of sensory afferents, are deeply conserved. Unexpectedly, the molecular programs specifying dorsal root ganglion (DRG) sensory subtypes diverge extensively from those of mammals. Although DRG neuron subtype specification and spinal connectivity rely on target-derived cues, skates employ distinct neurotrophin receptor and transcription factor identity codes. These findings support a model in which conserved spinal circuit architectures provide a stable scaffold that leverages flexible sensory neuron specification programs, enabling the evolutionary diversification of vertebrate somatosensory systems.

neuroscience↗

bioRxiv2023

Temporal and spatial analysis of astrocytes following stroke identifies novel drivers of reactivity

Astrocytes undergo robust gene expression changes in response to a variety of perturbations, including ischemic injury. How these transitions are affected by time, and how heterogeneous and spatially distinct various reactive astrocyte populations are, remain unclear. To address these questions, we performed spatial transcriptomics as well as single nucleus RNAseq of [~]138,000 mouse forebrain astrocytes at 1, 3, and 14 days after ischemic injury. We observed a widespread and temporally diverse response across many astrocyte subtypes. We identified astrocyte clusters unique in injury, including a transiently proliferative substate that may be BRCA1-dependent. We also found an interferon-responsive population that rapidly expands to the perilesion cortex at 1 day and persists up to 14 days post stroke. These lowly abundant, spatially restricted populations are likely functionally important in post-injury stabilization and resolution. These datasets offer valuable insights into injury-induced reactive astrocyte heterogeneity and can be used to guide functional interrogation of biologically meaningful reactive astrocyte substates to understand their pro- and anti-reparative functions following acute injuries such as stroke.

neuroscience↗

bioRxiv2022

De novo assembly and annotation of the singing mouse genome

BackgroundDeveloping genomic resources for a diverse range of species is an important step towards understanding the mechanisms underlying complex traits.Specifically, organisms that exhibit unique, accessible phenotypes-of-interests, allow researchers to address questions that may be ill-suited to traditional model organisms. We sequenced the genome and transcriptome of Alstons singing mouse (Scotinomys teguina), an emerging model for social cognition and vocal communication. In addition to producing advertisement songs used for mate attraction and male-male competition, these rodents are diurnal, live at high-altitudes, and are obligate insectivores, providing opportunities to explore diverse physiological, ecological, and evolutionary questions. ResultsUsing PromethION, Illumina, and PacBio sequencing, we produced an annotated genome and transcriptome, which were validated using gene expression and functional enrichment analyses. To assess the usefulness of our assemblies, we performed single nuclei sequencing on cells of the orofacial motor cortex, a brain region implicated in song coordination, identifying 12 cell types. ConclusionsThese resources will provide the opportunity to identify the molecular basis of complex traits in singing mice as well as to contribute data that can be used for large-scale comparative analyses.

genomics↗