Background: Class IIa HDACs are signal-dependent transcriptional corepressors that regulate cell differentiation programs and liver gluconeogenesis.Results: HDAC5 influences BMAL1 acetylation and interfering with normal expression levels of class IIa HDACs disrupts circadian rhythms.Conclusion: Class IIa HDACs regulate the robustness of cellular clocks and behavioral activity rhythms.Significance: Class IIa HDACs provide a conserved link between circadian clocks and metabolic signaling pathways.
Summary During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging in zebrafish reveals that differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord before axon initiation. These protrusions express Delta protein, consistent with the hypothesis they influence Notch signaling at a distance of several cell diameters. Experimental reduction of Laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that neuronal differentiation pattern is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers a stereotyped protrusive activity of newborn neurons that organize long-distance spatiotemporal patterning of differentiation.
Studies of non-apical progenitors (NAPs) have been largely limited to the developing mammalian cortex. They are postulated to generate the increase in neuron numbers that underlie mammalian brain expansion. Recently, NAPs have also been reported in the retina and central nervous system of non-mammalian species; in the latter, however, they remain poorly characterized. Here, we characterize NAP location along the zebrafish central nervous system during embryonic development, and determine their cellular and molecular characteristics and renewal capacity. We identified a small population of NAPs in the spinal cord, hindbrain and telencephalon of zebrafish embryos. Live-imaging analysis revealed at least two types of mitotic behaviour in the telencephalon: one NAP subtype retains the apical attachment during division, while another divides in a subapical position disconnected from the apical surface. All NAPs observed in spinal cord lost apical contact prior to mitoses. These NAPs express HuC and produce two neurons from a single division. Manipulation of Notch activity reveals that neurons and NAPs in the spinal cord use similar regulatory mechanisms. This work suggests that the majority of spinal NAPs in zebrafish share characteristics with basal progenitors in mammalian brains.
During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.
The Lim-kinase (LIMK) proteins are important for the regulation of the actin cytoskeleton, in particular the control of actin nucleation and depolymerisation via regulation of cofilin, and hence may control a large number of processes during development, including cell tensegrity, migration, cell cycling, and axon guidance. LIMK1/LIMK2 knockouts disrupt spinal cord morphogenesis and synapse formation but other tissues and developmental processes that require LIMK are yet to be fully determined. To identify tissues and cell-types that may require LIMK, we characterised the pattern of LIMK1 protein during mouse embryogenesis. We showed that LIMK1 displays an expression pattern that is temporally dynamic and tissue-specific. In several tissues LIMK1 is detected in cell-types that also express Wilms' tumour protein 1 and that undergo transitions between epithelial and mesenchymal states, including the pleura, epicardium, kidney nephrons, and gonads. LIMK1 was also found in a subset of cells in the dorsal retina, and in mesenchymal cells surrounding the peripheral nerves. This detailed study of the spatial and temporal expression of LIMK1 shows that LIMK1 expression is more dynamic than previously reported, in particular at sites of tissue-tissue interactions guiding multiple developmental processes. KeywordsLimk; Kidney; Heart; Epithelia-to-mesenchyme transition; Mesenchyme-to-epithelia transition; Eye; Testes The regulation of the actin cytoskeleton is essential for a very large number of cellular process including cellular migration, axon guidance, cell cycling, and polarity acquisition and maintenance. LIMK1 and LIMK2 control one of the fundamental aspects of actin dynamics, the depolymerisation of filamentous actin, by phosphorylation of ADF/cofilin (Arber et al., 1998). LIMK1 is primarily phosphorylated by the family of small RhoGTPases. When phosophorylated, LIMK1 in turn phosphorylates cofilin and blocks its ability to sever and de-nucleate actin filaments. Phosphorylation also inhibits the actin debranching properties that are normally exerted by cofilin competing with the actin-branching Arp2/3 complex (Arber et al., 1998;Bernard, 2007;Bernstein and Bamburg, 2010 Recently it has been shown that LIMK1 can act downstream of BMP signalling, modulate synapse stability by binding to BMP type II receptors, and control cell cycling by shuttling to the nucleus (Bernstein and Bamburg, 2010;Davila et al., 2007;Eaton and Davis, 2005;Hocking et al., 2009;Wen et al., 2007). In vivo and in vitro experiments on LIMK1 knockout mice have shown that the loss of LIMK1 results in neuronal growth cone, dendritic spine, and actin defects that are associated with abnormal hippocampal long term potentiation and synaptic changes (Meng et al., 2002). LIMK1 knockout mice also display elevated fear response and weakened learning abilities (Meng et al., 2002). Interestingly, the role of LIMK1 in controlling dendritic spine morphology is at least in part modulated by inhibition of LIMK1 through post-transcriptional microRNA-medi...
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.