Biology subjects

Taneyhill, L.

Publications and source records attributed to Taneyhill, L..

6 recordsLinked to original sources

bioRxiv2025

Proteomic profiling of Elp1-deficient trigeminal ganglia reveals disruption of neurotrophic and metabolic pathways in a familial dysautonomia mouse model

BackgroundElp1, a subunit of the Elongator complex, is essential for tRNA modification and neuronal development. Mutations in ELP1 underlie familial dysautonomia (FD), a disorder marked by sensory and autonomic neuropathy. While loss of Elp1 disrupts trigeminal ganglion formation and survival, the downstream molecular consequences remain poorly defined. ResultsWe performed quantitative proteomic profiling of trigeminal ganglia from Elp1 conditional knockout (CKO) and control embryos at E13.5. Across 5,650 detected proteins, 25 were significantly upregulated and 26 downregulated in Elp1 CKO embryos. EnrichR analysis revealed enrichment of upregulated proteins in amino acid transport and tRNA aminoacylation pathways, with links to neuromuscular and neuropathic diseases. Downregulated proteins were associated with RNA modification, cholesterol biosynthesis, and synaptic organization. Validation by immunohistochemistry confirmed decreased expression of the neurotrophic receptor Gfra3 and the neuropeptide Galanin, and increased levels of the chromatin regulator Chd1, in Elp1 CKO embryos relative to controls. ConclusionsThese findings demonstrate that Elp1 loss disrupts metabolic, RNA modification, and neurotrophic signaling pathways in the developing trigeminal ganglion. Proteomic analysis thus provides new insight into the molecular consequences of Elp1 deficiency and highlights candidate mechanisms contributing to sensory neuron vulnerability in FD.

developmental biology↗

bioRxiv2025

Multiple glycoforms of TrkA interact with N-cadherin during trigeminal ganglion neurodevelopment

The trigeminal ganglion is a component of the sensory nervous system that arises from neural crest and placode cells. The dual origin of the trigeminal ganglion leads to a heterogenous neuronal population that transmits somatosensory information from the face back to the brain. Proper trigeminal ganglion development relies, in part, on neurotrophic signaling, including interactions between Nerve Growth Factor and its cognate receptor, Tropomyosin receptor kinase A (TrkA), a receptor tyrosine kinase. Post-translational modifications, including glycosylation, play a crucial role in the ability of TrkA to reach the plasma membrane, yet the specific glycan profile and functional relevance of these modifications have not been characterized in sensory neurons in vivo. Here, we sought to characterize the different glycosylation events occurring on TrkA during trigeminal ganglion neurodevelopment. We discovered that multiple glycoforms of TrkA exist that correlate to partially and fully mature versions of the protein reported in vitro. Furthermore, we discovered that TrkA interacts with a cell adhesion molecule, N-cadherin, on membranes of trigeminal neurons, both in the cell bodies and axons. Based on the size of the TrkA bands that interact with N-cadherin, our results suggest these interactions are occurring both on the plasma membrane and intracellularly on the membrane of organelles. While interactions between receptor tyrosine kinases and cadherins have been shown in other contexts, our findings are the first to identify such an interaction in the trigeminal ganglion and suggest an important role for coordination between neurotrophic signaling and cell adhesion for proper neurodevelopment, both during TrkA protein maturation and during receptor tyrosine kinase signaling. Given that aberrant receptor tyrosine kinase and cadherin signaling is commonly implicated in neurodevelopmental disorders and cancer, understanding how these interactions are established during normal development may provide additional insight into their dysregulation during disease.

developmental biology↗

bioRxiv2024

The transcriptional landscape of the developing chick trigeminal ganglion

The trigeminal ganglion is a critical structure in the peripheral nervous system, responsible for transmitting sensations of touch, pain, and temperature from craniofacial regions to the brain. Trigeminal ganglion development depends upon intrinsic cellular programming as well as extrinsic signals exchanged by diverse cell populations. With its complex anatomy and dual cellular origin from cranial placodes and neural crest cells, the trigeminal ganglion offers a rich context for examining diverse biological processes, including cell migration, fate determination, adhesion, and axon guidance. Avian models have, so far, enabled key insights into craniofacial and peripheral nervous system development. Yet, the molecular mechanisms driving trigeminal ganglion formation and subsequent nerve growth remain elusive. In this study, we performed RNA-sequencing at multiple stages of chick trigeminal ganglion development and generated a novel transcriptomic dataset that has been curated to illustrate temporally dynamic gene expression patterns. This publicly available resource identifies major pathways involved in trigeminal gangliogenesis, particularly with respect to the condensation and maturation of placode-derived neurons, thus inviting new lines of research into the essential processes governing trigeminal ganglion development.

developmental biology↗

bioRxiv2024

N-cadherin facilitates trigeminal sensory neuron outgrowth and target tissue innervation

The trigeminal ganglion emerges from the condensation of two distinct precursor cell populations, cranial placodes and neural crest. While its dual cellular origin is well understood, the molecules underlying its formation remain relatively obscure. Trigeminal ganglion assembly is mediated, in part, by neural cadherin (N-cadherin), which is initially expressed by placodal neurons and required for their proper coalescence with neural crest cells. Axon outgrowth first occurs from placodal neurons, but as gangliogenesis proceeds, neural crest cells also differentiate into N-cadherin-expressing neurons, and both extend axons toward targets. However, the role of N-cadherin in axon outgrowth and target innervation has not been explored. Our data show that N-cadherin knockdown in chick trigeminal placode cells decreases trigeminal ganglion size, nerve growth, and target innervation in vivo, and reduces neurite complexity of neural crest-derived neurons in vitro. Furthermore, blocking N-cadherin-mediated adhesion prevents axon extension in most placodal neurons in vitro. Collectively, these findings reveal cell- and non-cell autonomous functions for N-cadherin, highlighting its critical role in mediating reciprocal interactions between neural crest- and placode-derived neurons throughout trigeminal ganglion development.

developmental biology↗

bioRxiv2022

Neurogenin 2 and Neuronal Differentiation 1 control proper development of the chick trigeminal ganglion and its nerve branches

The trigeminal ganglion contains the cell bodies of sensory neurons comprising cranial nerve V, which relays information related to pain, touch, and temperature from the face and head to the brain. Like other cranial ganglia, the trigeminal ganglion is composed of neuronal derivatives of two critical embryonic cell types, neural crest and placode cells. Neurogenesis within the cranial ganglia is promoted by Neurogenin 2 (Neurog2), which is expressed in trigeminal placode cells and their neuronal derivatives and transcriptionally activates neuronal differentiation genes like Neuronal Differentiation 1 (NeuroD1). Little is known, however, about the role of Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. To address this, we depleted Neurog2 and NeuroD1 from trigeminal placode cells with morpholinos and demonstrated that Neurog2 and NeuroD1 influence trigeminal ganglion development. While knockdown of both Neurog2 and NeuroD1 affected innervation of the eye, Neurog2 and NeuroD1 had opposite effects on ophthalmic nerve branch organization. Taken together, our results highlight, for the first time, functional roles for Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. These studies shed new light on the molecular mechanisms underlying trigeminal ganglion formation and may also provide insight into general cranial gangliogenesis and diseases of the peripheral nervous system.

developmental biology↗

bioRxiv2019

Connexin 43 impacts the chick premigratory cranial neural crest cell population without affecting the neural crest cell epithelial-to-mesenchymal transition

Gap junctions are intercellular channels that allow for the diffusion of small ions and solutes between coupled cells. Connexin 43 (Cx43), also known as Gap Junction Protein 1, is the most broadly expressed gap junction protein in vertebrate development. Cx43 is strongly expressed in premigratory cranial neural crest cells and is maintained throughout the neural crest cell epithelial-to-mesenchymal transition (EMT), but its function in these cells is not known. To this end, we have used a combination of in vivo and ex vivo live imaging with confocal microscopy, immunohistochemistry, and functional assays to assess gap junction formation, and Cx43 function, in chick premigratory cranial neural crest cells. Our results demonstrate that gap junctions exist between chick premigratory and migratory cranial neural crest cells, with Cx43 depletion inhibiting the function of gap junctions. While a reduction in Cx43 levels just prior to neural crest cell EMT did not affect EMT and subsequent emigration of neural crest cells from the neural tube, the size of the premigratory neural crest cell domain was decreased in the absence of any changes in cell proliferation or death. Collectively, these data identify a role for Cx43 within the chick premigratory cranial neural crest cell population prior to EMT and migration.

developmental biology↗