Previous studies have identified roles of the modulation of Notch activation by Fringe homologues in boundary formation and in regulating the differentiation of vertebrate thymocytes and Drosophila glial cells. We have investigated the role of Lunatic fringe (Lfng) expression during neurogenesis in the vertebrate neural tube. We find that in the zebrafish hindbrain, Lfng is expressed by progenitors in neurogenic regions and downregulated in cells that have initiated neuronal differentiation. Lfng is required cell autonomously in neural epithelial cells to limit the amount of neurogenesis and to maintain progenitors. By contrast, Lfng is not required for the role of Notch in interneuronal fate choice, which we show is mediated by Notch1a. The expression of Lfng does not require Notch activity, but rather is regulated downstream of proneural genes that are widely expressed by neural progenitors. These findings suggest that Lfng acts in a feedback loop downstream of proneural genes, which, by promoting Notch activation, maintains the sensitivity of progenitors to lateral inhibition and thus limits further proneural upregulation.KEY WORDS: Lateral inhibition, Neurogenesis, Neural progenitors, Notch, Fringe, Zebrafish Development 136, 2523Development 136, -2533Development 136, (2009 DEVELOPMENT 2524 differentiating cells in the cerebral cortex in mouse (Ishii et al., 2000). Furthermore, overexpression of Lfng in the chick neural tube was found to increase the number of neurons (de Bellard et al., 2007). These findings raise the possibility that modulation of Notch activity by Fringe homologues regulates neurogenesis in vertebrates.We set out to investigate the role of Lfng in the zebrafish nervous system, in which gene expression studies have suggested potential roles in boundary formation and/or neurogenesis. At early stages, lfng expression occurs at high levels in alternating segments in the hindbrain (Leve et al., 2001;Prince et al., 2001;Qiu et al., 2004), which by analogy with roles in other tissues could underlie boundary formation. In addition, lfng is expressed in dorsoventrally restricted domains in the neural tube (Prince et al., 2001) that could be associated with zones of neurogenesis. We show that Lfng limits neuronal differentiation and is required to maintain progenitor cells. Lfng acts cell autonomously in progenitors to inhibit their differentiation but, surprisingly, is upregulated downstream of proneural genes. We propose that Lfng acts in a feedback loop that maintains the competence of progenitor cells to receive lateral inhibition from differentiating neurons. MATERIALS AND METHODS Zebrafish linesWild-type, mib ta52b Schier et al., 1996), notch1a tp37 (Gray et al., 2001;Holley et al., 2002;van Eeden et al., 1996) and Tg(r3/r5-Gal4::UAS-RFP) embryos were produced and staged according to hours post fertilisation (hpf) and morphological criteria (Kimmel et al., 1995). MicroinjectionBlastomeres (1-to 4-cell) were microinjected with 0.45-1.8 pmol morpholino oligonucleotide (MO; Gene Tools). The ...
SUMMARYDuring central nervous system development, neural progenitors are patterned to form discrete neurogenic and non-neurogenic zones. In the zebrafish hindbrain, neurogenesis is organised by Fgf20a emanating from neurons located at each segment centre that inhibits neuronal differentiation in adjacent progenitors. Here, we have identified a molecular mechanism that clusters fgf20a-expressing neurons in segment centres and uncovered a requirement for this positioning in the regulation of neurogenesis. Disruption of hindbrain boundary cell formation alters the organisation of fgf20a-expressing neurons, consistent with a role of chemorepulsion from boundaries. The semaphorins Sema3fb and Sema3gb, which are expressed by boundary cells, and their receptor Nrp2a are required for clustering of fgf20a-expressing neurons at segment centres. The dispersal of fgf20a-expressing neurons that occurs following the disruption of boundaries or of Sema3fb/Sema3gb signalling leads to reduced FGF target gene expression in progenitors and an increased number of differentiating neurons. Sema3 signalling from boundaries thus links hindbrain segmentation to the positioning of fgf20a-expressing neurons that regulates neurogenesis.
The traditional Japanese health care custom recommends that a suitable volume of water is consumed. However, physiological and immunological mechanisms in support of this practice are unknown. Therefore, we conducted rat and rabbit in vivo experiments to investigate the effects of intragastric administration of distilled water on the jejunal-originated lymph flow and the concentrations and total flux of cells, albumin, long-chain fatty acids, and innate lymphoid cell 3 (ILC-3)-secreted interleukin-22 (IL-22) through mesenteric lymph vessels. The distribution and activity of ILC-3 in rat small intestine by water intake were evaluated using flow cytometry and RT-PCR. The intragastric administration of distilled water caused significant increases in rat mesenteric lymph flow and in the total flux of cells, albumin, long-chain fatty acids, and IL-22 through the lymph vessels. Intravenously injected Evans blue dye was rapidly transported into rabbit mesenteric lymph vessel and cisterna chyli. The distribution of ILC-3 and the expression of IL-22 mRNA were maximal in the lamina propria cells of the rat jejunum. No significant presence of ILC-3 in the lymph was observed in the control and under water intake conditions. In conclusion, the absorbed water in the jejunum is transported through mesenteric lymph vessels. The higher permeability of albumin in the jejunal microcirculation may play key roles in the transport of consumed water and the reservoir and transporter of long-chain fatty acids. Water intake also accelerates the transfer of IL-22 to the mesenteric lymph, which may contribute, in part, to maintaining and promoting the innate immunity in the body. NEW & NOTEWORTHY The higher permeability of albumin-mediated transport of water-soluble substances in mesenteric lymph vessels of the jejunum may have a large impact on the classic concept suggesting that water-soluble small molecules travel to the liver via the portal vein. ILC-3 is mainly housed in the lamina propria of the jejunum, especially its upper part. IL-22 released from the ILC-3 is also transported through mesenteric lymph in collaboration with the albumin-mediated movement of consumed water.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.