Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Cell Neurosci ; 17: 1158388, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091921

RESUMO

Since SARM1 mutations have been identified in human neurological disease, SARM1 inhibition has become an attractive therapeutic strategy to preserve axons in a variety of disorders of the peripheral (PNS) and central nervous system (CNS). While SARM1 has been extensively studied in neurons, it remains unknown whether SARM1 is present and functional in myelinating glia? This is an important question to address. Firstly, to identify whether SARM1 dysfunction in other cell types in the nervous system may contribute to neuropathology in SARM1 dependent diseases? Secondly, to ascertain whether therapies altering SARM1 function may have unintended deleterious impacts on PNS or CNS myelination? Surprisingly, we find that oligodendrocytes express sarm1 mRNA in the zebrafish spinal cord and that SARM1 protein is readily detectable in rodent oligodendrocytes in vitro and in vivo. Furthermore, activation of endogenous SARM1 in cultured oligodendrocytes induces rapid cell death. In contrast, in peripheral glia, SARM1 protein is not detectable in Schwann cells and satellite glia in vivo and sarm1/Sarm1 mRNA is detected at very low levels in Schwann cells, in vivo, in zebrafish and mouse. Application of specific SARM1 activators to cultured mouse Schwann cells does not induce cell death and nicotinamide adenine dinucleotide (NAD) levels remain unaltered suggesting Schwann cells likely contain no functionally relevant levels of SARM1. Finally, we address the question of whether SARM1 is required for myelination or myelin maintenance. In the zebrafish and mouse PNS and CNS, we show that SARM1 is not required for initiation of myelination and myelin sheath maintenance is unaffected in the adult mouse nervous system. Thus, strategies to inhibit SARM1 function to treat neurological disease are unlikely to perturb myelination in humans.

2.
Development ; 148(16)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34343262

RESUMO

Embryonic tissues are shaped by the dynamic behaviours of their constituent cells. To understand such cell behaviours and how they evolved, new approaches are needed to map out morphogenesis across different organisms. Here, we apply a quantitative approach to learn how the notochord forms during the development of amphioxus: a basally branching chordate. Using a single-cell morphometrics pipeline, we quantify the geometries of thousands of amphioxus notochord cells, and project them into a common mathematical space, termed morphospace. In morphospace, notochord cells disperse into branching trajectories of cell shape change, revealing a dynamic interplay between cell shape change and growth that collectively contributes to tissue elongation. By spatially mapping these trajectories, we identify conspicuous regional variation, both in developmental timing and trajectory topology. Finally, we show experimentally that, unlike ascidians but like vertebrates, posterior cell division is required in amphioxus to generate full notochord length, thereby suggesting this might be an ancestral chordate trait that is secondarily lost in ascidians. Altogether, our novel approach reveals that an unexpectedly complex scheme of notochord morphogenesis might have been present in the first chordates. This article has an associated 'The people behind the papers' interview.


Assuntos
Desenvolvimento Embrionário/fisiologia , Anfioxos/embriologia , Notocorda/embriologia , Organogênese/fisiologia , Análise de Célula Única/métodos , Animais , Divisão Celular/fisiologia , Forma Celular/fisiologia , Feminino , Masculino , Modelos Teóricos , Urocordados/embriologia
3.
Development ; 148(18)2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34086031

RESUMO

How force generated by the morphogenesis of one tissue impacts the morphogenesis of other tissues to achieve an elongated embryo axis is not well understood. The notochord runs along the length of the somitic compartment and is flanked on either side by somites. Vacuolating notochord cells undergo a constrained expansion, increasing notochord internal pressure and driving its elongation and stiffening. Therefore, the notochord is appropriately positioned to play a role in mechanically elongating the somitic compartment. We used multi-photon cell ablation to remove specific regions of the zebrafish notochord and quantify the impact on axis elongation. We show that anterior expansion generates a force that displaces notochord cells posteriorly relative to adjacent axial tissues, contributing to the elongation of segmented tissue during post-tailbud stages. Unexpanded cells derived from progenitors at the posterior end of the notochord provide resistance to anterior notochord cell expansion, allowing for stress generation along the anterior-posterior axis. Therefore, notochord cell expansion beginning in the anterior, and addition of cells to the posterior notochord, act as temporally coordinated morphogenetic events that shape the zebrafish embryo anterior-posterior axis.


Assuntos
Embrião não Mamífero/fisiologia , Desenvolvimento Embrionário/fisiologia , Notocorda/fisiologia , Peixe-Zebra/fisiologia , Animais , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Morfogênese/fisiologia , Notocorda/metabolismo , Somitos/metabolismo , Somitos/fisiologia , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
4.
Development ; 146(10)2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31023877

RESUMO

The caudal lateral epiblast of mammalian embryos harbours bipotent progenitors that contribute to the spinal cord and the paraxial mesoderm in concert with the body axis elongation. These progenitors, called neural mesodermal progenitors (NMPs), are identified as cells that co-express Sox2 and T/brachyury, a criterion used to derive NMP-like cells from embryonic stem cells in vitro However, unlike embryonic NMPs, these progenitors do not self-renew. Here, we find that the protocols that yield NMP-like cells in vitro initially produce a multipotent population that, in addition to NMPs, generates progenitors for the lateral plate and intermediate mesoderm. We show that epiblast stem cells (EpiSCs) are an effective source of these multipotent progenitors, which are further differentiated by a balance between BMP and Nodal signalling. Importantly, we show that NMP-like cells derived from EpiSCs exhibit limited self-renewal in vitro and a gene expression signature like their embryonic counterparts.


Assuntos
Padronização Corporal/fisiologia , Camadas Germinativas/citologia , Células-Tronco Neurais/metabolismo , Animais , Padronização Corporal/genética , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem da Célula , Camadas Germinativas/metabolismo , Mesoderma/citologia , Mesoderma/metabolismo , Células-Tronco Neurais/citologia , Fatores de Transcrição SOXB1/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...