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1.
Dev Cell ; 58(5): 361-375.e5, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36841243

RESUMO

Despite their barrier function, epithelia can locally lose their integrity to create physiological openings during morphogenesis. The mechanisms driving the formation of these epithelial breaks are only starting to be investigated. Here, we study the formation of the zebrafish nostril (the olfactory orifice), which opens in the skin epithelium to expose the olfactory neurons to external odorant cues. Combining live imaging, drug treatments, laser ablation, and tissue-specific functional perturbations, we characterize a mechanical interplay between olfactory placode neurons and the skin, which plays a crucial role in the formation of the orifice: the neurons pull on the overlying skin cells in an actomyosin-dependent manner which, in combination with a local reorganization of the skin epithelium, triggers the opening of the orifice. This work identifies an original mechanism to break an epithelial sheet, in which an adjacent group of cells mechanically assists the epithelium to induce its local rupture.


Assuntos
Actomiosina , Peixe-Zebra , Animais , Neurônios/fisiologia , Epitélio , Ectoderma , Mucosa Olfatória
2.
EMBO Rep ; 23(2): e52963, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34889034

RESUMO

While the chemical signals guiding neuronal migration and axon elongation have been extensively studied, the influence of mechanical cues on these processes remains poorly studied in vivo. Here, we investigate how mechanical forces exerted by surrounding tissues steer neuronal movements and axon extension during the morphogenesis of the olfactory placode in zebrafish. We mainly focus on the mechanical contribution of the adjacent eye tissue, which develops underneath the placode through extensive evagination and invagination movements. Using quantitative analysis of cell movements and biomechanical manipulations, we show that the developing eye exerts lateral traction forces on the olfactory placode through extracellular matrix, mediating proper morphogenetic movements and axon extension within the placode. Our data shed new light on the key participation of intertissue mechanical interactions in the sculpting of neuronal circuits.


Assuntos
Condutos Olfatórios , Peixe-Zebra , Animais , Axônios/fisiologia , Ectoderma , Morfogênese , Neurogênese , Condutos Olfatórios/anatomia & histologia , Condutos Olfatórios/fisiologia , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/fisiologia
3.
J Cell Biol ; 219(7)2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32364583

RESUMO

Through a genetic screen in zebrafish, we identified a mutant with disruption to myelin in both the CNS and PNS caused by a mutation in a previously uncharacterized gene, slc12a2b, predicted to encode a Na+, K+, and Cl- (NKCC) cotransporter, NKCC1b. slc12a2b/NKCC1b mutants exhibited a severe and progressive pathology in the PNS, characterized by dysmyelination and swelling of the periaxonal space at the axon-myelin interface. Cell-type-specific loss of slc12a2b/NKCC1b in either neurons or myelinating Schwann cells recapitulated these pathologies. Given that NKCC1 is critical for ion homeostasis, we asked whether the disruption to myelinated axons in slc12a2b/NKCC1b mutants is affected by neuronal activity. Strikingly, we found that blocking neuronal activity completely prevented and could even rescue the pathology in slc12a2b/NKCC1b mutants. Together, our data indicate that NKCC1b is required to maintain neuronal activity-related solute homeostasis at the axon-myelin interface, and the integrity of myelinated axons.


Assuntos
Axônios/metabolismo , Bainha de Mielina/metabolismo , Neurônios/metabolismo , Células de Schwann/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/genética , Proteínas de Peixe-Zebra/genética , Potenciais de Ação , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Axônios/efeitos dos fármacos , Axônios/ultraestrutura , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Mutação , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/ultraestrutura , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/metabolismo , Sistema Nervoso Periférico/patologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/ultraestrutura , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Bloqueadores dos Canais de Sódio/toxicidade , Membro 2 da Família 12 de Carreador de Soluto/deficiência , Tetrodotoxina/toxicidade , Peixe-Zebra , Proteínas de Peixe-Zebra/deficiência
5.
Nat Neurosci ; 21(1): 19-23, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29230058

RESUMO

During myelination, individual oligodendrocytes initially over-produce short myelin sheaths, which are either retracted or stabilized. By live-imaging oligodendrocyte Ca2+ activity in vivo, we find that high-amplitude, long-duration Ca2+ transients in sheaths prefigure retractions, mediated by calpain. Following stabilization, myelin sheaths grow along axons, and we find that higher-frequency Ca2+ transient activity in sheaths precedes faster elongation. Our data implicate local Ca2+ signaling in regulating distinct stages of myelination.


Assuntos
Axônios/fisiologia , Cálcio/metabolismo , Bainha de Mielina/metabolismo , Oligodendroglia/fisiologia , Medula Espinal/fisiologia , Acrilatos/farmacologia , Animais , Animais Geneticamente Modificados , Calpaína/antagonistas & inibidores , Larva , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Bainha de Mielina/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , RNA Mensageiro/metabolismo , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismo , Fatores de Tempo , Imagem com Lapso de Tempo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
6.
Curr Biol ; 26(11): 1447-55, 2016 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-27161502

RESUMO

Regulation of myelination by oligodendrocytes in the CNS has important consequences for higher-order nervous system function (e.g., [1-4]), and there is growing consensus that neuronal activity regulates CNS myelination (e.g., [5-9]) through local axon-oligodendrocyte synaptic-vesicle-release-mediated signaling [10-12]. Recent analyses have indicated that myelination along axons of distinct neuronal subtypes can differ [13, 14], but it is not known whether regulation of myelination by activity is common to all neuronal subtypes or only some. This limits insight into how specific neurons regulate their own conduction. Here, we use a novel fluorescent fusion protein reporter to study myelination along the axons of distinct neuronal subtypes over time in zebrafish. We find that the axons of reticulospinal and commissural primary ascending (CoPA) neurons are among the first myelinated in the zebrafish CNS. To investigate how activity regulates myelination by different neuronal subtypes, we express tetanus toxin (TeNT) in individual reticulospinal or CoPA neurons to prevent synaptic vesicle release. We find that the axons of individual tetanus toxin expressing reticulospinal neurons have fewer myelin sheaths than controls and that their myelin sheaths are 50% shorter than controls. In stark contrast, myelination along tetanus-toxin-expressing CoPA neuron axons is entirely normal. These results indicate that while some neuronal subtypes modulate myelination by synaptic vesicle release to a striking degree in vivo, others do not. These data have implications for our understanding of how different neurons regulate myelination and thus their own function within specific neuronal circuits.


Assuntos
Bainha de Mielina/fisiologia , Transmissão Sináptica , Vesículas Sinápticas/metabolismo , Peixe-Zebra/fisiologia , Animais , Animais Geneticamente Modificados
7.
Brain Res ; 1641(Pt A): 149-161, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-26498877

RESUMO

Myelinated axons with nodes of Ranvier are an evolutionary elaboration common to essentially all jawed vertebrates. Myelin made by Schwann cells in our peripheral nervous system and oligodendrocytes in our central nervous system has been long known to facilitate rapid energy efficient nerve impulse propagation. However, it is now also clear, particularly in the central nervous system, that myelin is not a simple static insulator but that it is dynamically regulated throughout development and life. New myelin sheaths can be made by newly differentiating oligodendrocytes, and mature myelin sheaths can be stimulated to grow again in the adult. Furthermore, numerous studies in models from fish to man indicate that neuronal activity can affect distinct stages of oligodendrocyte development and the process of myelination itself. This begs questions as to how these effects of activity are mediated at a cellular and molecular level and whether activity-driven adaptive myelination is a feature common to all myelinated axons, or indeed all oligodendrocytes, or is specific to cells or circuits with particular functions. Here we review the recent literature on this topic, elaborate on the key outstanding questions in the field, and look forward to future studies that incorporate investigations in systems from fish to man that will provide further insight into this fundamental aspect of nervous system plasticity. This article is part of a Special Issue entitled SI: Myelin Evolution.


Assuntos
Bainha de Mielina/fisiologia , Plasticidade Neuronal , Animais , Evolução Biológica , Humanos , Aprendizagem/fisiologia , Neurônios/fisiologia
8.
Nat Neurosci ; 18(5): 628-30, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25849985

RESUMO

The myelination of axons by oligodendrocytes markedly affects CNS function, but how this is regulated by neuronal activity in vivo is not known. We found that blocking synaptic vesicle release impaired CNS myelination by reducing the number of myelin sheaths made by individual oligodendrocytes during their short period of formation. We also found that stimulating neuronal activity increased myelin sheath formation by individual oligodendrocytes. These data indicate that neuronal activity regulates the myelinating capacity of single oligodendrocytes.


Assuntos
Bainha de Mielina/fisiologia , Neurônios/fisiologia , Oligodendroglia/citologia , Vesículas Sinápticas/metabolismo , Animais , Contagem de Células , Quimera , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Antagonistas de Receptores de GABA-A/farmacologia , Bainha de Mielina/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Pentilenotetrazol/farmacologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Toxina Tetânica/farmacologia , Peixe-Zebra/embriologia
9.
J Neurosci ; 33(40): 15726-34, 2013 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-24089481

RESUMO

Although mRNA was once thought to be excluded from the axonal compartment, the existence of protein synthesis in growing or regenerating axons in culture is now generally accepted. However, its extent and functional importance remain a subject of intense investigation. Furthermore, unambiguous evidence of mRNA axonal transport and local translation in vivo, in the context of a whole developing organism is still lacking. Here, we provide direct evidence of the presence of mRNAs of the tubb5, nefma, and stmnb2 genes in several types of axons in the developing zebrafish (Danio rerio) embryo, with frequent accumulation at the growth cone. We further show that axonal localization of mRNA is a specific property of a subset of genes, as mRNAs of the huc and neurod genes, abundantly expressed in neurons, were not found in axons. We set up a reporter system in which the 3' untranslated region (UTR) of candidate mRNA, fused to a fluorescent protein coding sequence, was expressed in isolated neurons of the zebrafish embryo. Using this reporter, we identified in the 3'UTR of tubb5 mRNA a motif necessary and sufficient for axonal localization. Our work thus establishes the zebrafish as a model system to study axonal transport in a whole developing vertebrate organism, provides an experimental frame to assay this transport in vivo and to study its mechanisms, and identifies a new zipcode involved in axonal mRNA localization.


Assuntos
Axônios/metabolismo , Cones de Crescimento/metabolismo , Neurônios/metabolismo , Transporte de RNA/fisiologia , RNA Mensageiro/metabolismo , Peixe-Zebra/metabolismo , Animais , Transporte Axonal/fisiologia , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Estatmina/genética , Estatmina/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
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