scholarly journals Neuroblast sensory quiescence depends of vascular cytoneme contacts and sensory neuronal differentiation requires initiation of blood flow

2019 ◽  
Author(s):  
Laura Taberner ◽  
Aitor Bañón ◽  
Berta Alsina

SummaryIn many organs, stem cell function depends on the communication with their niche partners. Cranial sensory neurons develop in close proximity to blood vessels, however whether vasculature is an integral component of their niches is yet unknown. Here, two separate, novel roles for vasculature in cranial sensory neurogenesis in zebrafish are uncovered. The first involves precise spatiotemporal endothelial-neuroblast cytoneme contacts and Dll4-Notch signalling to restrain neuroblast proliferation. Secondly, we find that blood flow onset triggers a transcriptional response to modify neuroblast metabolic status and is required for sensory neuron differentiation. In contrast, no role of sensory neurogenesis in vascular development is found, suggesting a unidirectional signalling from vasculature to sensory neuroblasts. Altogether, we demonstrate that the cranial vasculature constitutes a hitherto unrecognized niche component of the sensory ganglia that regulates the pace of their growth and differentiation dynamics.Highlights♦ Vasculature is part of the cranial sensory ganglia niche and regulates neurogenesis.♦ Cytoneme contacts between endothelial cells and sensory neuroblasts are required for neuroblast quiescence.♦ Endothelial Dll4 and neuroblast Notch1 signal to regulate the growth of cranial sensory ganglia.♦ Initiation of blood flow triggers a transcriptional metabolic switch and sensory neuronal differentiation.

BioFactors ◽  
2004 ◽  
Vol 21 (1-4) ◽  
pp. 15-18 ◽  
Author(s):  
Ichiro Matsumoto ◽  
Shugo Nakamura ◽  
Yasufumi Emori ◽  
Soichi Arai ◽  
Keiko Abe

2014 ◽  
Vol 199 (4) ◽  
pp. 278-293 ◽  
Author(s):  
Mohammed Abu El-Magd ◽  
Ayman A. Saleh ◽  
Foad Farrag ◽  
Reda M. Abd El-Aziz ◽  
Haytham A. Ali ◽  
...  

2021 ◽  
Author(s):  
Maria Sancho ◽  
Nicholas R. Klug ◽  
Amreen Mughal ◽  
Thomas J. Heppner ◽  
David Hill-Eubanks ◽  
...  

SUMMARYThe dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuro/glial-derived compounds that regulate regional and global cerebral perfusion. The membrane potential (VM) of vascular cells serves as the essential output in this scenario, linking brain activity to vascular function. The ATP-sensitive K+ channel (KATP) is a key regulator of vascular VM in other beds, but whether brain capillaries possess functional KATP channels remains unknown. Here, we demonstrate that brain capillary ECs and pericytes express KATP channels that robustly control VM. We further show that the endogenous mediator adenosine acts through A2A receptors and the Gs/cAMP/PKA pathway to activate capillary KATP channels. Moreover, KATP channel stimulation in vivo causes vasodilation and increases cerebral blood flow (CBF). These findings establish the presence of KATP channels in cECs and pericytes and suggest their significant influence on CBF.HIGHLIGHTSCapillary network cellular components—endothelial cells and pericytes—possess functional KATP channels.Activation of KATP channels causes profound hyperpolarization of capillary cell membranes.Capillary KATP channels are activated by exogenous adenosine via A2A receptors and cAMP-dependent protein kinase.KATP channel activation by adenosine or synthetic openers increases cerebral blood flow.


2020 ◽  
Vol 98 (9) ◽  
pp. 1301-1317
Author(s):  
Rinal Sahputra ◽  
Emma A Murphy ◽  
Ruth Forman ◽  
Iris Mair ◽  
Muhammad Z. H. Fadlullah ◽  
...  

Abstract The IgMi mouse has normal B cell development; its B cells express an IgM B cell receptor but cannot class switch or secrete antibody. Thus, the IgMi mouse offers a model system by which to dissect out antibody-dependent and antibody-independent B cell function. Here, we provide the first detailed characterisation of the IgMi mouse post-Trichuris muris (T. muris) infection, describing expulsion phenotype, cytokine production, gut pathology and changes in T regulatory cells, T follicular helper cells and germinal centre B cells, in addition to RNA sequencing (RNA seq) analyses of wild-type littermates (WT) and mutant B cells prior to and post infection. IgMi mice were susceptible to a high-dose infection, with reduced Th2 cytokines and elevated B cell-derived IL-10 in mesenteric lymph nodes (MLN) compared to controls. A low-dose infection regime revealed IgMi mice to have significantly more apoptotic cells in the gut compared to WT mice, but no change in intestinal inflammation. IL-10 levels were again elevated. Collectively, this study showcases the potential of the IgMi mouse as a tool for understanding B cell biology and suggests that the B cell plays both antibody-dependent and antibody-independent roles post high- and low-dose T. muris infection. Key messages During a high-dose T. muris infection, B cells are important in maintaining the Th1/Th2 balance in the MLN through an antibody-independent mechanism. High levels of IL-10 in the MLN early post-infection, and the presence of IL-10-producing B cells, correlates with susceptibility to T. muris infection. B cells maintain gut homeostasis during chronic T. muris infection via an antibody-dependent mechanism.


2004 ◽  
Vol 126 (1) ◽  
pp. 98-102 ◽  
Author(s):  
Ichiro Matsumoto ◽  
Nami Nagamatsu ◽  
Soichi Arai ◽  
Yasufumi Emori ◽  
Keiko Abe

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