RESUMO
Chemosensation and mechanosensation cover an enormous spectrum of processes by which animals use information from the environment to adapt their behavior. For pragmatic reasons, these sensory modalities are commonly investigated independently. Recent advances, however, have revealed numerous situations in which they function together to control animals' actions. Highlighting examples from diverse vertebrates and invertebrates, we first discuss sensory receptors and neurons that have dual roles in the detection of chemical and mechanical stimuli. Next we present cases where peripheral chemosensory and mechanosensory pathways are discrete but intimately packaged to permit coordinated reception of external cues. Finally, we consider how chemical and mechanical signals converge in central neural circuitry to enable multisensory integration. These insights demonstrate how investigation of the interplay between different sensory modalities is key to a more holistic and realistic understanding of sensory-guided behaviors.
Assuntos
Neurônios/metabolismo , Transdução de Sinais/fisiologia , Animais , Humanos , Modelos NeurológicosRESUMO
CXCL12/CXCR4 signaling has been reported to regulate three essential processes for the establishment of neural networks in different neuronal systems: neuronal migration, cell positioning and axon wiring. However, it is not known whether it regulates the development of A9-A10 tyrosine hydroxylase positive (TH(+)) midbrain dopaminergic (mDA) neurons. We report here that Cxcl12 is expressed in the meninges surrounding the ventral midbrain (VM), whereas CXCR4 is present in NURR1(+) mDA precursors and mDA neurons from E10.5 to E14.5. CXCR4 is activated in NURR1(+) cells as they migrate towards the meninges. Accordingly, VM meninges and CXCL12 promoted migration and neuritogenesis of TH(+) cells in VM explants in a CXCR4-dependent manner. Moreover, in vivo electroporation of Cxcl12 at E12.5 in the basal plate resulted in lateral migration, whereas expression in the midline resulted in retention of TH(+) cells in the IZ close to the midline. Analysis of Cxcr4(-/-) mice revealed the presence of VM TH(+) cells with disoriented processes in the intermediate zone (IZ) at E11.5 and marginal zone (MZ) at E14. Consistently, pharmacological blockade of CXCR4 or genetic deletion of Cxcr4 resulted in an accumulation of TH(+) cells in the lateral aspect of the IZ at E14, indicating that CXCR4 is required for the radial migration of mDA neurons in vivo. Altogether, our findings demonstrate that CXCL12/CXCR4 regulates the migration and orientation of processes in A9-A10 mDA neurons.
Assuntos
Movimento Celular , Quimiocina CXCL12/metabolismo , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais , Animais , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Feminino , Deleção de Genes , Masculino , Meninges/citologia , Meninges/metabolismo , Mesencéfalo/citologia , Mesencéfalo/embriologia , Mesencéfalo/metabolismo , Camundongos , Camundongos Mutantes , Neuritos/metabolismo , Neurogênese , Fosforilação , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Chemosensory tissues exhibit significant between-species variability, yet the evolution of gene expression and cell types underlying this diversity remain poorly understood. To address these questions, we conducted transcriptomic analyses of five chemosensory tissues from six Drosophila species and integrated the findings with single-cell datasets. While stabilizing selection predominantly shapes chemosensory transcriptomes, thousands of genes in each tissue have evolved expression differences. Genes that have changed expression in one tissue have often changed in multiple other tissues but at different past epochs and are more likely to be cell type-specific than unchanged genes. Notably, chemosensory-related genes have undergone widespread expression changes, with numerous species-specific gains/losses including novel chemoreceptors expression patterns. Sex differences are also pervasive, including a D. melanogaster-specific excess of male-biased expression in sensory and muscle cells in its forelegs. Together, our analyses provide new insights for understanding evolutionary changes in chemosensory tissues at both global and individual gene levels.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Feminino , Masculino , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Filogenia , Evolução MolecularRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Although much is known about the migration of interneurons from the subpallium to the cortex, our understanding of the mechanisms controlling their precise integration within the cortex is still limited. Here, we have investigated in detail the behavior of GABAergic interneurons as they first enter the developing cortex by using time-lapse videomicroscopy, slice culture, and in utero experimental manipulations and analysis of mouse mutants. We found that interneurons actively avoid the cortical plate for a period of approximately 48 h after reaching the pallium; during this time, interneurons disperse tangentially through the marginal and subventricular zones. Perturbation of CXCL12/CXCR4 signaling causes premature cortical plate invasion by cortical interneurons and, in the long term, disrupts their laminar and regional distribution. These results suggest that regulation of cortical plate invasion by GABAergic interneurons is a key event in cortical development, because it directly influences the coordinated formation of appropriate glutamatergic and GABAergic neuronal assemblies.
Assuntos
Movimento Celular/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Quimiocina CXCL12/metabolismo , Interneurônios/citologia , Interneurônios/metabolismo , Receptores CXCR4/metabolismo , Animais , Comunicação Celular , Técnicas de Cocultura , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais , Ácido gama-Aminobutírico/metabolismoRESUMO
Through analysis of the Drosophila ionotropic receptors (IRs), a family of variant ionotropic glutamate receptors, we reveal that most IRs are expressed in peripheral neuron populations in diverse gustatory organs in larvae and adults. We characterise IR56d, which defines two anatomically-distinct neuron classes in the proboscis: one responds to carbonated solutions and fatty acids while the other represents a subset of sugar- and fatty acid-sensing cells. Mutational analysis indicates that IR56d, together with the broadly-expressed co-receptors IR25a and IR76b, is essential for physiological responses to carbonation and fatty acids, but not sugars. We further demonstrate that carbonation and fatty acids both promote IR56d-dependent attraction of flies, but through different behavioural outputs. Our work provides a toolkit for investigating taste functions of IRs, defines a subset of these receptors required for carbonation sensing, and illustrates how the gustatory system uses combinatorial expression of sensory molecules in distinct neurons to coordinate behaviour.
Assuntos
Carbonatos/metabolismo , Proteínas de Drosophila/metabolismo , Receptores Ionotrópicos de Glutamato/metabolismo , Animais , Comportamento Animal/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster , Ácidos Graxos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Receptores Ionotrópicos de Glutamato/genética , Paladar/genética , Paladar/fisiologiaRESUMO
Textural properties provide information on the ingestibility, digestibility and state of ripeness or decay of sources of nutrition. Compared with our understanding of the chemosensory assessment of food, little is known about the mechanisms of texture detection. Here we show that Drosophila melanogaster can discriminate food texture, avoiding substrates that are either too hard or too soft. Manipulations of food substrate properties and flies' chemosensory inputs indicate that texture preferences are revealed only in the presence of an appetitive stimulus, but are not because of changes in nutrient accessibility, suggesting that animals discriminate the substrates' mechanical characteristics. We show that texture preference requires NOMPC, a TRP-family mechanosensory channel. NOMPC localizes to the sensory dendrites of neurons housed within gustatory sensilla, and is essential for their mechanosensory-evoked responses. Our results identify a sensory pathway for texture detection and reveal the behavioural integration of chemical and physical qualities of food.
Assuntos
Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Mecanorreceptores/fisiologia , Mecanotransdução Celular/fisiologia , Sensilas/fisiologia , Canais de Potencial de Receptor Transitório/fisiologia , Animais , Animais Geneticamente Modificados , Dendritos/fisiologia , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Masculino , Sensilas/citologiaRESUMO
Neural circuits in the cerebral cortex consist of excitatory pyramidal cells and inhibitory interneurons. These two main classes of cortical neurons follow largely different genetic programs, yet they assemble into highly specialized circuits during development following a very precise choreography. Previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, but the molecular nature of these factors has remained elusive. Here, we identified Neuregulin 3 (Nrg3) as a chemoattractive factor expressed by developing pyramidal cells that guides the allocation of cortical interneurons in the developing cortical plate. Gain- and loss-of-function approaches reveal that Nrg3 modulates the migration of interneurons into the cortical plate in a process that is dependent on the tyrosine kinase receptor ErbB4. Perturbation of Nrg3 signaling in conditional mutants leads to abnormal lamination of cortical interneurons. Nrg3 is therefore a critical mediator in the assembly of cortical inhibitory circuits.
Assuntos
Neurônios GABAérgicos/metabolismo , Interneurônios/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Animais , Movimento Celular/fisiologia , Córtex Cerebral/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurregulinas , Células Piramidais/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptor ErbB-4/metabolismo , Transdução de Sinais/fisiologiaRESUMO
The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110ß in NPC, only p110ß participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110ß blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110ß is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110ß is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex.
Assuntos
Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/enzimologia , Animais , Ativação Enzimática/efeitos dos fármacos , Interneurônios/citologia , Interneurônios/efeitos dos fármacos , Interneurônios/enzimologia , Janus Quinases/metabolismo , Camundongos , Células-Tronco Neurais/efeitos dos fármacos , Células Piramidais/citologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/enzimologia , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismoRESUMO
The chemokine Cxcl12 binds Cxcr4 and Cxcr7 receptors to control cell migration in multiple biological contexts, including brain development, leukocyte trafficking, and tumorigenesis. Both receptors are expressed in the CNS, but how they cooperate during migration has not been elucidated. Here, we used the migration of cortical interneurons as a model to study this process. We found that Cxcr4 and Cxcr7 are coexpressed in migrating interneurons, and that Cxcr7 is essential for chemokine signaling. Intriguingly, this process does not exclusively involve Cxcr7, but most critically the modulation of Cxcr4 function. Thus, Cxcr7 is necessary to regulate Cxcr4 protein levels, thereby adapting chemokine responsiveness in migrating cells. This demonstrates that a chemokine receptor modulates the function of another chemokine receptor by controlling the amount of protein that is made available for signaling at the cell surface.