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1.
PLoS Genet ; 18(5): e1010178, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35511794

RESUMEN

Animals integrate changes in external and internal environments to generate behavior. While neural circuits detecting external cues have been mapped, less is known about how internal states like hunger are integrated into behavioral outputs. Here, we use the nematode C. elegans to examine how changes in internal nutritional status affect chemosensory behaviors. We show that acute food deprivation leads to a reversible decline in repellent, but not attractant, sensitivity. This behavioral change requires two conserved transcription factors MML-1 (MondoA) and HLH-30 (TFEB), both of which translocate from the intestinal nuclei to the cytoplasm during food deprivation. Next, we identify the insulin-like peptide INS-31 as a candidate ligand relaying food-status signals from the intestine to other tissues. Further, we show that neurons likely use the DAF-2 insulin receptor and AGE-1/PI-3 Kinase, but not DAF-16/FOXO to integrate these intestine-released peptides. Altogether, our study shows how internal food status signals are integrated by transcription factors and intestine-neuron signaling to generate flexible behaviors via the gut-brain axis.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Factores de Transcripción Forkhead , Insulina , Intestinos , Asunción de Riesgos , Factores de Transcripción/genética
2.
Dev Biol ; 346(2): 296-309, 2010 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-20692250

RESUMEN

The processes of myelination remain incompletely understood but are of profound biomedical importance owing to the several dysmyelinating and demyelinating disorders known in humans. Here, we analyze the zebrafish puma mutant, isolated originally for pigment pattern defects limited to the adult stage. We show that puma mutants also have late-arising defects in Schwann cells of the peripheral nervous system, locomotor abnormalities, and sex-biased defects in adult craniofacial morphology. Using methods of positional cloning, we identify a critical genetic interval harboring two alpha tubulin loci, and we identify a chemically induced missense mutation in one of these, tubulin alpha 8-like 3a (tuba8l3a). We demonstrate tuba8l3a expression in the central nervous system (CNS), leading us to search for defects in the development of oligodendrocytes, the myelinating cells of the CNS. We find gross reductions in CNS myelin and oligodendrocyte numbers in adult puma mutants, and these deficits are apparent already during the larval-to-adult transformation. By contrast, analyses of embryos and early larvae reveal a normal complement of oligodendrocytes that nevertheless fail to localize normal amounts of myelin basic protein (mbp) mRNA in cellular processes, and fail to organize these processes as in the wild-type. This study identifies the puma mutant as a valuable model for studying microtubule-dependent events of myelination, as well as strategies for remyelination in the adult.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Mutación , Oligodendroglía/citología , Proteínas Proto-Oncogénicas/genética , Células de Schwann/citología , Tubulina (Proteína)/genética , Proteínas de Pez Cebra/genética , Pez Cebra/embriología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Secuencia de Bases , Sistema Nervioso Central/embriología , Sistema Nervioso Central/metabolismo , Embrión no Mamífero/metabolismo , Datos de Secuencia Molecular , Oligodendroglía/metabolismo , Filogenia , Proteínas Proto-Oncogénicas/metabolismo , ARN Mensajero/metabolismo , Células de Schwann/metabolismo , Pigmentación de la Piel/genética , Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
3.
Invert Neurosci ; 14(2): 71-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24395463

RESUMEN

Insulin signaling plays a critical role in coupling external changes to animal physiology and behavior. Despite remarkable conservation in the insulin signaling pathway components across species, divergence in the mechanism and function of the signal is evident. Focusing on recent findings from C. elegans, D. melanogaster and mammals, we discuss the role of insulin signaling in regulating adult neuronal function and behavior. In particular, we describe the transcription-dependent and transcription-independent aspects of insulin signaling across these three species. Interestingly, we find evidence of diverse mechanisms underlying complex networks of peptide action in modulating nervous system function.


Asunto(s)
Evolución Biológica , Insulina/metabolismo , Sistema Nervioso/metabolismo , Péptidos/metabolismo , Animales , Anélidos , Dípteros , Humanos , Insulina/química , Mamíferos
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