Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell non-autonomous requirement of p75 in the development of geniculate oral sensory neurons.

ABSTRACT: 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; p75^fx/fx) or in neural crest-derived cells (P0-Cre; p75^fx/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; p75^fx/fx or P0-Cre; p75^fx/fx mice. Electrophysiological analyses demonstrated that Phox2b-Cre; p75^fx/fx mice had normal taste and oral tactile responses. There was a modest but significant loss of fungiform taste buds in Phox2b-Cre; p75^fx/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.

SUBMITTER: Tang T

PROVIDER: S-EPMC7747618 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The transcription factor Phox2b distinguishes between oral and non-oral sensory neurons in the geniculate ganglion.

Project description:Many basic characteristics of gustatory neurons remain unknown, partly due to the absence of specific markers. Some neurons in the geniculate ganglion project to taste regions in the oral cavity, whereas others innervate the outer ear. We hypothesized that the transcription factor Phox2b would identify oral cavity-projecting neurons in the geniculate ganglion. To test this possibility, we characterized mice in which Phox2b-Cre mediated gene recombination labeled neurons with tdTomato. Nerve labeling revealed that all taste neurons projecting through the chorda tympani (27%) and greater superficial petrosal nerves (15%) expressed Phox2b during development, whereas non-oral somatosensory neurons (58%) in the geniculate ganglion did not. We found tdTomato-positive innervation within all taste buds. Most (57%) of the fungiform papillae had labeled innervation only in taste buds, whereas 43% of the fungiform papillae also had additional labeled innervation to the papilla epithelium. Chorda tympani nerve transection eliminated all labeled innervation to taste buds, but most of the additional innervation in the fungiform papillae remained. Some of these additional fibers also expressed tyrosine hydroxylase, suggesting a sympathetic origin. Consistent with this, both sympathetic and parasympathetic fibers innervating blood vessels and salivary glands contained tdTomato labeling. Phox2b-tdTomato labels nerve fascicles in the tongue of the developing embryo and demonstrates a similar stereotyped branching pattern DiI-labeling.

| S-EPMC5912919 | biostudies-literature

Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons.

Project description:Neurofibromatosis type 1 (NF1) is among the most common genetic disorders of humans and is caused by loss of neurofibromin, a large and highly conserved protein whose only known function is to serve as a GTPase-Activating Protein (GAP) for Ras. However, most Drosophila NF1 mutant phenotypes, including an overall growth deficiency, are not readily modified by manipulating Ras signaling strength, but are rescued by increasing signaling through the cAMP-dependent protein kinase A pathway. This has led to suggestions that NF1 has distinct Ras- and cAMP-related functions. Here we report that the Drosophila NF1 growth defect reflects a non-cell-autonomous requirement for NF1 in larval neurons that express the R-Ras ortholog Ras2, that NF1 is a GAP for Ras1 and Ras2, and that a functional NF1-GAP catalytic domain is both necessary and sufficient for rescue. Moreover, a Drosophila p120RasGAP ortholog, when expressed in the appropriate cells, can substitute for NF1 in growth regulation. Our results show that loss of NF1 can give rise to non-cell-autonomous developmental defects, implicate aberrant Ras-mediated signaling in larval neurons as the primary cause of the NF1 growth deficiency, and argue against the notion that neurofibromin has separable Ras- and cAMP-related functions.

| S-EPMC1686607 | biostudies-literature

Non-canonical Ret signaling augments p75-mediated cell death in developing sympathetic neurons.

Project description:Programmed cell death (PCD) is an evolutionarily conserved process critical in sculpting many organ systems, yet the underlying mechanisms remain poorly understood. Here, we investigated the interactions of pro-survival and pro-apoptotic receptors in PCD using the sympathetic nervous system as a model. We demonstrate that Ret, a receptor tyrosine kinase required for the survival of many neuronal populations, is restricted to a subset of degenerating neurons that rapidly undergo apoptosis. Pro-apoptotic conditions induce Ret to associate with the death receptor p75. Genetic deletion of p75 within Ret+ neurons, and deletion of Ret during PCD, inhibit apoptosis both in vitro and in vivo. Mechanistically, Ret inhibits nerve growth factor (NGF)-mediated survival of sympathetic neurons. Removal of Ret disrupts NGF-mediated TrkA ubiquitination, leading to increased cell surface levels of TrkA, thereby potentiating survival signaling. Additionally, Ret deletion significantly impairs p75 regulated intramembrane proteolysis cleavage, leading to reduced activation of downstream apoptotic effectors. Collectively, these results indicate that Ret acts non-canonically to augment p75-mediated apoptosis.

| S-EPMC6122988 | biostudies-literature

Cell-autonomous and non-cell-autonomous roles for IRF6 during development of the tongue.

Project description:Interferon regulatory factor 6 (IRF6) encodes a highly conserved helix-turn-helix DNA binding protein and is a member of the interferon regulatory family of DNA transcription factors. Mutations in IRF6 lead to isolated and syndromic forms of cleft lip and palate, most notably Van der Woude syndrome (VWS) and Popliteal Ptyerigium Syndrome (PPS). Mice lacking both copies of Irf6 have severe limb, skin, palatal and esophageal abnormalities, due to significantly altered and delayed epithelial development. However, a recent report showed that MCS9.7, an enhancer near Irf6, is active in the tongue, suggesting that Irf6 may also be expressed in the tongue. Indeed, we detected Irf6 staining in the mesoderm-derived muscle during development of the tongue. Dual labeling experiments demonstrated that Irf6 was expressed only in the Myf5+ cell lineage, which originates from the segmental paraxial mesoderm and gives rise to the muscles of the tongue. Fate mapping of the segmental paraxial mesoderm cells revealed a cell-autonomous Irf6 function with reduced and poorly organized Myf5+ cell lineage in the tongue. Molecular analyses showed that the Irf6-/- embryos had aberrant cytoskeletal formation of the segmental paraxial mesoderm in the tongue. Fate mapping of the cranial neural crest cells revealed non-cell-autonomous Irf6 function with the loss of the inter-molar eminence. Loss of Irf6 function altered Bmp2, Bmp4, Shh, and Fgf10 signaling suggesting that these genes are involved in Irf6 signaling. Based on these data, Irf6 plays important cell-autonomous and non-cell-autonomous roles in muscular differentiation and cytoskeletal formation in the tongue.

| S-EPMC3579850 | biostudies-literature

Non-cell-autonomous planar cell polarity propagation in the auditory sensory epithelium of vertebrates.

Project description:Sensory epithelia of the inner ear require a coordinated alignment of hair cell stereociliary bundles as an essential element of mechanoreceptive function. Hair cell bundle alignment is mediated by core planar cell polarity (PCP) proteins, such as Vangl2, that localize asymmetrically to the circumference of the cell near its apical surface. During early phases of cell orientation in the chicken basilar papilla (BP), Vangl2 is present at supporting cell junctions that lie orthogonal to the polarity axis. Several days later, there is a striking shift in the Vangl2 pattern associated with hair cells that reorient towards the distal (apical) end of the organ. How the localization of PCP proteins transmits planar polarity information across the developing sensory epithelium remains unclear. To address this question, the normal asymmetric localization of Vangl2 was disrupted by overexpressing Vangl2 in clusters of cells. The BP was infected with replication-competent retrovirus encoding Vangl2 prior to hair cell differentiation. Virus-infected cells showed normal development of individual stereociliary bundles, indicating that asymmetry was established at the cellular level. Yet, bundles were misoriented in ears infected with Vangl2 virus but not Wnt5a virus. Notably, Vangl2 misexpression did not randomize bundle orientations but rather generated larger variations around a normal mean angle. Cell clusters with excess Vangl2 could induce non-autonomous polarity disruptions in wild-type neighboring cells. Furthermore, there appears to be a directional bias in the propagation of bundle misorientation that is towards the abneural edge of the epithelium. Finally, regional bundle reorientation was inhibited by Vangl2 overexpression. In conclusion, ectopic Vangl2 protein causes inaccurate local propagation of polarity information, and Vangl2 acts in a non-cell-autonomous fashion in the sensory system of vertebrates.

| S-EPMC3052742 | biostudies-literature

Oral Sensory Neurons of the Geniculate Ganglion That Express Tyrosine Hydroxylase Comprise a Subpopulation That Contacts Type II and Type III Taste Bud Cells.

Project description:Oral sensory neurons of the geniculate ganglion (GG) innervate taste papillae and buds on the tongue and soft palate. Electrophysiological recordings of these neurons and fibers revealed complexity in the number of unique response profiles observed, suggesting there are several distinct neuronal subtypes. Molecular descriptions of these subpopulations are incomplete. We report here the identification of a subpopulation of GG oral sensory neurons in mice by expression of tyrosine hydroxylase (TH). TH-expressing geniculate neurons represent 10-20% of oral sensory neurons and these neurons innervate taste buds in fungiform and anterior foliate taste papillae on the surface of the tongue, as well as taste buds in the soft palate. While 35-50% of taste buds on the tongue are innervated by these TH+ neurons, 100% of soft palate taste buds are innervated. These neurons did not have extragemmal processes outside of taste buds and did not express the mechanosensory neuron-associated gene Ret, suggesting they are chemosensory and not somatosensory neurons. Within taste buds, TH-expressing fibers contacted both Type II and Type III cells, raising the possibility that they are responsive to more than one taste quality. During this analysis we also identified a rare TH+ taste receptor cell type that was found in only 12-25% of taste buds and co-expressed TRPM5, suggesting it was a Type II cell. Taken together, TH-expressing GG oral sensory neurons innervate taste buds preferentially in the soft palate and contact Type II and Type III taste bud receptor cells.

| S-EPMC9581578 | biostudies-literature

Jedi-1 deficiency increases sensory neuron excitability through a non-cell autonomous mechanism.

Project description:The dorsal root ganglia (DRG) house the primary afferent neurons responsible for somatosensation, including pain. We previously identified Jedi-1 (PEAR1/MEGF12) as a phagocytic receptor expressed by satellite glia in the DRG involved in clearing apoptotic neurons during development. Here, we further investigated the function of this receptor in vivo using Jedi-1 null mice. In addition to satellite glia, we found Jedi-1 expression in perineurial glia and endothelial cells, but not in sensory neurons. We did not detect any morphological or functional changes in the glial cells or vasculature of Jedi-1 knockout mice. Surprisingly, we did observe changes in DRG neuron activity. In neurons from Jedi-1 knockout (KO) mice, there was an increase in the fraction of capsaicin-sensitive cells relative to wild type (WT) controls. Patch-clamp electrophysiology revealed an increase in excitability, with a shift from phasic to tonic action potential firing patterns in KO neurons. We also found alterations in the properties of voltage-gated sodium channel currents in Jedi-1 null neurons. These results provide new insight into the expression pattern of Jedi-1 in the peripheral nervous system and indicate that loss of Jedi-1 alters DRG neuron activity indirectly through an intercellular interaction between non-neuronal cells and sensory neurons.

| S-EPMC6987110 | biostudies-literature

Non-cell-autonomous inhibition of photoreceptor development by Dip3.

Project description:We show here that the Drosophila MADF/BESS domain transcription factor Dip3, which is expressed in differentiating photoreceptors, regulates neuronal differentiation in the compound eye. Loss of Dip3 activity in photoreceptors leads to an extra photoreceptor in many ommatidia, while ectopic expression of Dip3 in non-neuronal cells results in photoreceptor loss. These findings are consistent with the idea that Dip3 is required non-cell autonomously to block extra photoreceptor formation. Dip3 may mediate the spatially restricted potentiation of Notch (N) signaling since the Dip3 misexpression phenotype is suppressed by reducing N signaling and misexpression of Dip3 leads to ectopic activity of a N-responsive enhancer. Analysis of mosaic ommatidia suggests that no specific photoreceptor must be mutant to generate the mutant phenotype. Remarkably, however, mosaic pupal ommatidia with three or fewer Dip3(+) photoreceptors always differentiate an extra photoreceptor, while those with four or more Dip3(+) photoreceptors never differentiate an extra photoreceptor. These findings are consistent with the notion that Dip3 in photoreceptors activates a heretofore unsuspected diffusible ligand that may work in conjunction with the N pathway to prevent a subpopulation of undifferentiated cells from choosing a neuronal fate.

| S-EPMC2614221 | biostudies-literature

<i>Serping1/</i>C1 Inhibitor Affects Cortical Development in a Cell Autonomous and Non-cell Autonomous Manner.

Project description:Current knowledge regarding regulation of radial neuronal migration is mainly focused on intracellular molecules. Our unbiased screen aimed at identification of non-cell autonomous mechanisms involved in this process detected differential expression of Serping1 or C1 inhibitor, which is known to inhibit the initiation of the complement cascade. The complement cascade is composed of three pathways; the classical, lectin, and the alternative pathway; the first two are inhibited by C1 inhibitor, and all three converge at the level of C3. Knockdown or knockout of Serping1 affected neuronal stem cell proliferation and impaired neuronal migration in mice. Knockdown of Serping1 by in utero electroporation resulted in a migration delay of the electroporated cells as well as their neighboring cells demonstrating a non-cell autonomous effect. Cellular polarity was also affected. Most importantly, expression of protein components mimicking cleaved C3 rescued the knockdown of Serping1, indicating complement pathway functionality. Furthermore, we propose that this activity is mediated mainly via the complement peptide C5a receptors. Whereas addition of a selective C3a receptor agonist was minimally effective, the addition of a dual C3aR/C5a receptor agonist significantly rescued Serping1 knockdown-mediated neuronal migration defects. Our findings suggest that modulating Serping1 levels in the developing brain may affect the complement pathway in a complex way. Collectively, our findings demonstrate an unorthodox activity for the complement pathway during brain development.

| S-EPMC5472692 | biostudies-literature

Brain-derived neurotrophic factor mediates non-cell-autonomous regulation of sensory neuron position and identity.

Project description:During development, neurons migrate considerable distances to reside in locations that enable their individual functional roles. Whereas migration mechanisms have been extensively studied, much less is known about how neurons remain in their ideal locations. We sought to identify factors that maintain the position of postmigratory dorsal root ganglion neurons, neural crest derivatives for which migration and final position play an important developmental role. We found that an early developing population of sensory neurons maintains the position of later born dorsal root ganglia neurons in an activity-dependent manner. Further, inhibiting or increasing the function of brain-derived neurotrophic factor induces or prevents, respectively, migration of dorsal root ganglia neurons out of the ganglion to locations where they acquire a new identity. Overall, the results demonstrate that neurotrophins mediate non-cell-autonomous maintenance of position and thereby the identity of differentiated neurons.

| S-EPMC3319702 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data