Biology subjects

Chaverra, M.

Publications and source records attributed to Chaverra, M..

4 recordsLinked to original sources

bioRxiv2025

Two classes of amine/glutamate multi-transmitter neurons innervate Drosophila internal male reproductive organs

The essential outcome of a successful mating is the transfer of genetic material from males to females in sexually reproducing animals from insects to mammals. In males, this culminates in ejaculation, a precisely timed sequence of organ contractions driven by the concerted activity of interneurons, sensory neurons, and motor neurons. Although central command circuits that trigger copulation have been mapped, the motor architecture and the chemical logic that couple specific neuronal subclasses to organ specific contractility, seminal fluid secretion, and sperm emission remain largely uncharted. This gap in knowledge limits our ability to explain how neural circuits adapt to varying contexts and how their failure contributes to infertility. Here we present an in-depth anatomical and functional analysis of the motor neurons that innervate the internal male reproductive tract of Drosophila melanogaster. We identify two classes of multi-transmitter motor neurons based on neurotransmitter usage, namely octopamine and glutamate neurons (OGNs) and serotonin and glutamate neurons (SGNs), each with a biased pattern of innervation: SGNs predominate in the accessory glands, OGNs in the ejaculatory duct, with equal contributions of each to the seminal vesicles. Both classes co-express vesicular transporters for glutamate (vGlut) and amines (vMAT), confirming their dual chemical identity. Their target organs differentially express receptors for glutamate, octopamine, and serotonin, suggesting combinatorial neuromodulation of contractility. Functional manipulations show that SGNs are essential for male fertility but OGNs are dispensable. Glutamatergic transmission from both classes is also dispensable for fertility. These findings provide the first high-resolution map linking multi-transmitter motor neurons to specific reproductive organs, reveal an unexpected division of labor between serotonergic and octopaminergic signaling pathways, and establish a framework for dissecting conserved neural principles that govern ejaculation and male fertility.

neuroscience↗

bioRxiv2024

Community-wide interactions sustain life in geothermal spring habitats

We investigated an alga-dominated geothermal spring community in Yellowstone National Park, USA. Our goal was to determine how cells cope with abiotic stressors during diurnal sampling that spanned over two orders of magnitude in solar irradiance. We report a community level response to toxic metal resistance and energy cycling that spans the three domains of life. Arsenic detoxification is accomplished via complementary gene expression by different lineages. Photosynthesis is dominated by Cyanidioschyzon, with the mixotroph, Galdieria, relegated to nighttime heterotrophy. Many key functions, including the cell cycle, are strongly regulated by diurnal light fluctuations. These results demonstrate that biotic interactions are highly structured in extreme habitats. We suggest this was also the case on the early Earth when geothermal springs were cradles of microbial life, prior to the origin of eukaryotes.

evolutionary biology↗

bioRxiv2023

Reduction of retinal ganglion cell death in mouse models of familial dysautonomia using AAV-mediated gene therapy and splicing modulators

Familial dysautonomia (FD) is a rare neurodevelopmental and neurodegenerative disease caused by a splicing mutation in the Elongator Acetyltransferase Complex Subunit 1 (ELP1) gene. The reduction in ELP1 mRNA and protein leads to the death of retinal ganglion cells (RGCs) and visual impairment in all FD patients. Currently, patient symptoms are managed, but there is no treatment for the disease. We sought to test the hypothesis that restoring levels of Elp1 would thwart the death of RGCs in FD. To this end, we tested the effectiveness of two therapeutic strategies for rescuing RGCs. Here we provide proof-of-concept data that gene replacement therapy and small molecule splicing modifiers effectively reduce the death of RGCs in mouse models for FD and provide pre-clinical data foundation for translation to FD patients.

neuroscience↗

bioRxiv2022

Elp1 is required for development of visceral sensory peripheral and central circuitry

Cardiovascular instability and a blunted respiratory drive in hypoxic conditions, are hallmark features of the genetic sensory and autonomic neuropathy, familial dysautonomia (FD). FD results from a mutation in the gene ELP1, whose encoded protein is a scaffolding subunit of the six subunit Elongator complex. In mice, we and others have shown that Elp1 is essential for the normal development of neural crest derived-dorsal root ganglia (DRG) sensory neurons. Whether Elp1 is also required for development of ectodermal placode-derived visceral sensory receptors which are required for normal baroreception and chemosensory responses, has not been investigated. Using mouse models for FD, our data indicate that in fact the entire circuitry underlying baroreception and chemoreception is impaired due to a requirement for Elp1 not only in the visceral sensory neuron ganglia, but also for normal peripheral target innervation, and in their CNS synaptic partners in the medulla. Thus Elp1 is required in both placode- and neural crest-derived sensory neurons and its reduction aborts the normal development of neuronal circuitry essential for autonomic homeostasis and interoception. Summary statementDue to faulty afferent sensory signaling, patients with Familial dysautonomia (FD) have a diminished sensory arm of the baroreflex which would normally modulate blood pressure, and they have a blunted response to hypoxia and hypercapnia (Norcliffe-Kaufmann et al. 2010). Using mouse models for FD, we reveal here the underlying pathology which may underlie these severely impaired homeostatic reflex pathways in FD.

neuroscience↗