Browsing by Author "Donnelly, Christopher R."

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    Cell non-autonomous requirement of p75 in the development of geniculate oral sensory neurons
    (Springer Nature, 2020-12-17) Tang, Tao; Donnelly, Christopher R.; Shah, Amol A.; Bradley, Robert M.; Mistretta, Charlotte M.; Pierchala, Brian A.; Anatomy and Cell Biology, School of Medicine
    During development of the peripheral taste system, oral sensory neurons of the geniculate ganglion project via the chorda tympani nerve to innervate taste buds in fungiform papillae. Germline deletion of the p75 neurotrophin receptor causes dramatic axon guidance and branching deficits, leading to a loss of geniculate neurons. To determine whether the developmental functions of p75 in geniculate neurons are cell autonomous, we deleted p75 specifically in Phox2b + oral sensory neurons (Phox2b-Cre; p75fx/fx) or in neural crest-derived cells (P0-Cre; p75fx/fx) and examined geniculate neuron development. In germline p75−/− mice half of all geniculate neurons were lost. The proportion of Phox2b + neurons, as compared to Phox2b-pinna-projecting neurons, was not altered, indicating that both populations were affected similarly. Chorda tympani nerve recordings demonstrated that p75−/− mice exhibit profound deficits in responses to taste and tactile stimuli. In contrast to p75−/− mice, there was no loss of geniculate neurons in either Phox2b-Cre; p75fx/fx or P0-Cre; p75fx/fx mice. Electrophysiological analyses demonstrated that Phox2b-Cre; p75fx/fx mice had normal taste and oral tactile responses. There was a modest but significant loss of fungiform taste buds in Phox2b-Cre; p75fx/fx mice, although there was not a loss of chemosensory innervation of the remaining fungiform taste buds. Overall, these data suggest that the developmental functions of p75 are largely cell non-autonomous and require p75 expression in other cell types of the chorda tympani circuit.
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    Correction to: Probing the multimodal fungiform papilla: complex peripheral nerve endings of chorda tympani taste and mechanosensitive fibers before and after Hedgehog pathway inhibition
    (Springer, 2022) Donnelly, Christopher R.; Kumari, Archana; Li, Libo; Vesela, Iva; Bradley, Robert M.; Mistretta, Charlotte M.; Pierchala, Brian A.; Anatomy, Cell Biology and Physiology, School of Medicine
    This corrects the article "Probing the multimodal fungiform papilla: complex peripheral nerve endings of chorda tympani taste and mechanosensitive fibers before and after Hedgehog pathway inhibition" in Cell Tissue Res, volume 387 on page 225.
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    Plasma membrane localization of the GFL receptor components: a nexus for receptor crosstalk
    (Springer, 2020-08-07) Donnelly, Christopher R.; Pierchala, Brian A.; Anatomy and Cell Biology, School of Medicine
    The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) comprise a group of four homologous and potent growth factors that includes GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN). The survival, growth, and mitotic activities of the GFLs are conveyed by a single receptor tyrosine kinase, Ret. The GFLs do not bind directly to Ret in order to activate it, and instead bind with high affinity to glycerophosphatidylinositol (GPI)-anchored coreceptors called the GDNF family receptor-αs (GFRαs). Several mechanisms have recently been identified that influence the trafficking of Ret and GFRαs in and out of the plasma membrane, thereby affecting their availability for ligand binding, as well as their levels by targeting to degradative pathways. This review describes these mechanisms and their powerful effects on GFL signaling and function. We also describe the recent discovery that p75 and Ret form a signaling complex, also regulated by plasma membrane shuttling, that either enhances GFL survival signals or p75 pro-apoptotic signals, dependent on the cellular context.
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    Probing the multimodal fungiform papilla: complex peripheral nerve endings of chorda tympani taste and mechanosensitive fibers before and after Hedgehog pathway inhibition
    (Springer, 2022) Donnelly, Christopher R.; Kumari, Archana; Li, Libo; Vesela, Iva; Bradley, Robert M.; Mistretta, Charlotte M.; Pierchala, Brian A.; Anatomy, Cell Biology and Physiology, School of Medicine
    The fungiform papilla (FP) is a gustatory and somatosensory structure incorporating chorda tympani (CT) nerve fibers that innervate taste buds (TB) and also contain somatosensory endings for touch and temperature. Hedgehog (HH) pathway inhibition eliminates TB, but CT innervation remains in the FP. Importantly, after HH inhibition, CT neurophysiological responses to taste stimuli are eliminated, but tactile responses remain. To examine CT fibers that respond to tactile stimuli in the absence of TB, we used Phox2b-Cre; Rosa26LSL-TdTomato reporter mice to selectively label CT fibers with TdTomato. Normally CT fibers project in a compact bundle directly into TB, but after HH pathway inhibition, CT fibers reorganize and expand just under the FP epithelium where TB were. This widened expanse of CT fibers coexpresses Synapsin-1, β-tubulin, S100, and neurofilaments. Further, GAP43 expression in these fibers suggests they are actively remodeling. Interestingly, CT fibers have complex terminals within the apical FP epithelium and in perigemmal locations in the FP apex. These extragemmal fibers remain after HH pathway inhibition. To identify tactile end organs in FP, we used a K20 antibody to label Merkel cells. In control mice, K20 was expressed in TB cells and at the base of epithelial ridges outside of FP. After HH pathway inhibition, K20 + cells remained in epithelial ridges but were eliminated in the apical FP without TB. These data suggest that the complex, extragemmal nerve endings within and disbursed under the apical FP are the mechanosensitive nerve endings of the CT that remain after HH pathway inhibition.