Biology subjects

Reilly, M. B.

Publications and source records attributed to Reilly, M. B..

3 recordsLinked to original sources

bioRxiv2025

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons

Neuron-specific morphology and function are fundamentally tied to differences in gene expression across the nervous system. We previously generated a single cell RNA-seq (scRNA-Seq) dataset for every anatomical neuron class in the C. elegans hermaphrodite. Here we present a complementary set of bulk RNA-seq samples for 52 of the 118 canonical neuron classes in C. elegans. We show that the bulk RNA-seq dataset captures both lowly expressed and noncoding RNAs that are not detected in the scRNA-Seq profile, but also includes false positives due to contamination by other cell types. We present an analytical strategy that integrates the two datasets, preserving both the specificity of scRNA-Seq data and the sensitivity of bulk RNA-Seq. We show that this integrated dataset enhances the sensitivity and accuracy of transcript detection and differential gene analysis. In addition, we show that the bulk RNA-Seq data set detects differentially expressed non-coding RNAs across neuron types, including multiple families of non-polyadenylated transcripts. We propose that our approach provides a new strategy for interrogating gene expression by bridging the gap between bulk and single cell methodologies for transcriptomic studies. We suggest that these datasets advance the goal of delineating the mechanisms that define morphology and connectivity in the nervous system.

genomics↗

bioRxiv2022

Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification

Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In the nematode Caenorhabditis elegans, each individual neuron class is defined by the expression of unique combinations of homeobox genes, prompting the question of whether each neuron class indeed requires a homeobox gene for its proper identity specification. We present here progress in addressing this question by extending previous mutant analysis of homeobox gene family members and describing multiple examples of homeobox gene function in different parts of the C. elegans nervous system. To probe homeobox function, we make use of a number of reporter gene tools, including a novel multicolor reporter transgene, NeuroPAL, which permits simultaneous monitoring of the execution of multiple differentiation programs throughout the entire nervous system. Using these tools, we add to the previous characterization of homeobox gene function by identifying neuronal differentiation defects for 12 homeobox genes in 20 distinct neuron classes that are mostly unrelated by location, function and lineage history. 10 of these 20 neuron classes had no homeobox gene function ascribed to them before, while in the other 10 neuron classes, we extend the combinatorial code of transcription factors required for specifying terminal differentiation programs. Furthermore, we demonstrate that in a particular lineage, homeotic identity transformations occur upon loss of a homeobox gene and we show that these transformations are the result of changes in homeobox codes. Combining the present with past analysis, 111 of the 118 neuron classes of C. elegans are now known to require a homeobox gene for proper execution of terminal differentiation programs. Such broad deployment indicates that homeobox function in neuronal identity specification may be an ancestral feature of animal nervous systems.

neuroscience↗

bioRxiv2020

Molecular topography of an entire nervous system

Nervous systems are constructed from a deep repertoire of neuron types but the underlying gene expression programs that specify individual neuron identities are poorly understood. To address this deficit, we have produced an expression profile of all 302 neurons of the C. elegans nervous system that matches the single cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses unique codes of [~]23 neuropeptide-encoding genes and [~]36 neuropeptide receptors thus pointing to an expansive "wireless" signaling network. To demonstrate the utility of this uniquely comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression across the nervous system and (2) reveal adhesion proteins with potential roles in synaptic specificity and process placement. These data are available at cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity and function throughout the C. elegans nervous system.

neuroscience↗