scholarly journals Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3001051
Author(s):  
Albert Zhang ◽  
Ziqiang Guan ◽  
Kyle Ockerman ◽  
Pengyuan Dong ◽  
Jiansheng Guo ◽  
...  

Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Caenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conserved cis-Golgi membrane protein eas-1/GOLT1B negatively regulates glial growth. We found that eas-1 inhibits a conserved E3 ubiquitin ligase rnf-145/RNF145, which, in turn, promotes nuclear activation of sbp-1/ SREBP, a key regulator of sterol and fatty acid synthesis, to restrict cell growth. At early developmental stages, rnf-145 in the cis-Golgi network inhibits sbp-1 activation to promote the growth of glia, and when animals reach the adult stage, this inhibition is released through an eas-1-dependent shuttling of rnf-145 from the cis-Golgi to the trans-Golgi network to stop glial growth. Furthermore, we identified long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA), as downstream products of the eas-1-rnf-145-sbp-1 pathway that functions to prevent the overgrowth of glia. Together, our findings reveal a novel and potentially conserved mechanism underlying glial size control.

1994 ◽  
Vol 28 (4) ◽  
pp. 376-379 ◽  
Author(s):  
Leonard Friedman ◽  
Dennis W. Gaines ◽  
Richard F. Newell ◽  
Arlen O. Sager ◽  
Roger N. Matthews ◽  
...  

As part of a larger study designed to characterize the early developmental stages of the Hormel-Hanford strain miniature pig, whole body, brain, kidney, liver, pancreas and spleen from male animals were examined for weight increases from one to 196 days, the approximate age of maturity. At 196 days, body weights had increased to 82.5 times the weight at day 1; increases in organ weights were greatest for spleen, less and similar for kidney, liver and pancreas, and the least for brain. Little change in relative organ weights was noted, except for the brain where an almost steady decrease occurred starting from 7 days after birth.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Nicolás M. Díaz ◽  
Luis P. Morera ◽  
Daniela M. Verra ◽  
María A. Contin ◽  
Mario E. Guido

The retina is a key component of the vertebrate circadian system; it is responsible for detecting and transmitting the environmental illumination conditions (day/night cycles) to the brain that synchronize the circadian clock located in the suprachiasmatic nucleus (SCN). For this, retinal ganglion cells (RGCs) project to the SCN and other nonvisual areas. In the chicken, intrinsically photosensitive RGCs (ipRGCs) expressing the photopigment melanopsin (Opn4) transmit photic information and regulate diverse nonvisual tasks. In nonmammalian vertebrates, two genes encodeOpn4: theXenopus(Opn4x) and the mammalian (Opn4m) orthologs. RGCs express bothOpn4genes but are not the only inner retinal cells expressingOpn4x: horizontal cells (HCs) also do so. Here, we further characterize primary cultures of both populations of inner retinal cells (RGCs and HCs) expressingOpn4x. The expression of this nonvisual photopigment, as well as that for different circadian markers such as the clock genesBmal1,Clock,Per2, andCry1, and the key melatonin synthesizing enzyme, arylalkylamineN-acetyltransferase (AA-NAT), appears very early in development in both cell populations. The results clearly suggest that nonvisual Opn4 photoreceptors and endogenous clocks converge all together in these inner retinal cells at early developmental stages.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009794
Author(s):  
Stefano Suzzi ◽  
Reiner Ahrendt ◽  
Stefan Hans ◽  
Svetlana A. Semenova ◽  
Avinash Chekuru ◽  
...  

LRRK2 gain-of-function is considered a major cause of Parkinson’s disease (PD) in humans. However, pathogenicity of LRRK2 loss-of-function in animal models is controversial. Here we show that deletion of the entire zebrafish lrrk2 locus elicits a pleomorphic transient brain phenotype in maternal-zygotic mutant embryos (mzLrrk2). In contrast to lrrk2, the paralog gene lrrk1 is virtually not expressed in the brain of both wild-type and mzLrrk2 fish at different developmental stages. Notably, we found reduced catecholaminergic neurons, the main target of PD, in specific cell populations in the brains of mzLrrk2 larvae, but not adult fish. Strikingly, age-dependent accumulation of monoamine oxidase (MAO)-dependent catabolic signatures within mzLrrk2 brains revealed a previously undescribed interaction between LRRK2 and MAO biological activities. Our results highlight mzLrrk2 zebrafish as a tractable tool to study LRRK2 loss-of-function in vivo, and suggest a link between LRRK2 and MAO, potentially of relevance in the prodromic stages of PD.


2018 ◽  
Vol 31 (10) ◽  
pp. 1032-1047 ◽  
Author(s):  
Chihiro Miura ◽  
Katsushi Yamaguchi ◽  
Ryohei Miyahara ◽  
Tatsuki Yamamoto ◽  
Masako Fuji ◽  
...  

Achlorophylous and early developmental stages of chorolophylous orchids are highly dependent on carbon and other nutrients provided by mycorrhizal fungi, in a nutritional mode termed mycoheterotrophy. Previous findings have implied that some common properties at least partially underlie the mycorrhizal symbioses of mycoheterotrophic orchids and that of autotrophic arbuscular mycorrhizal (AM) plants; however, information about the molecular mechanisms of the relationship between orchids and their mycorrhizal fungi is limited. In this study, we characterized the molecular basis of an orchid-mycorrhizal (OM) symbiosis by analyzing the transcriptome of Bletilla striata at an early developmental stage associated with the mycorrhizal fungus Tulasnella sp. The essential components required for the establishment of mutual symbioses with AM fungi or rhizobia in most terrestrial plants were identified from the B. striata gene set. A cross-species gene complementation analysis showed one of the component genes, calcium and calmodulin-dependent protein kinase gene CCaMK in B. striata, retains functional characteristics of that in AM plants. The expression analysis revealed the activation of homologs of AM-related genes during the OM symbiosis. Our results suggest that orchids possess, at least partly, the molecular mechanisms common to AM plants.


2019 ◽  
Vol 116 (45) ◽  
pp. 22598-22608 ◽  
Author(s):  
Wenjie Huang ◽  
Zhe Liu ◽  
Fan Yang ◽  
Huan Zhou ◽  
Xin Yong ◽  
...  

Pontocerebellar hypoplasia (PCH) is a group of neurological disorders that affect the development of the brain, in particular, the pons and cerebellum. Homozygous mutations of TBC1D23 have been found recently to lead to PCH; however, the underlying molecular mechanisms remain unclear. Here, we show that the crystal structure of the TBC1D23 C-terminal domain adopts a Pleckstrin homology domain fold and selectively binds to phosphoinositides, in particular, PtdIns(4)P, through one surface while binding FAM21 via the opposite surface. Mutation of key residues of TBC1D23 or FAM21 selectively disrupts the endosomal vesicular trafficking toward the Trans-Golgi Network. Finally, using the zebrafish model, we show that PCH patient-derived mutants, impacting either phosphoinositide binding or FAM21 binding, lead to abnormal neuronal growth and brain development. Taken together, our data provide a molecular basis for the interaction between TBC1D23 and FAM21, and suggest a plausible role for PtdIns(4)P in the TBC1D23-mediating endosome-to-TGN trafficking pathway. Defects in this trafficking pathway are, at least partially, responsible for the pathogenesis of certain types of PCH.


2021 ◽  
Author(s):  
Athena Demertzi ◽  
Aaron Kucyi ◽  
Georgios A. Keliris ◽  
Susan Whitfield-Gabrieli

The brainʼs spontaneous activity changes across states of consciousness. A particular consciousness-mediated brain configuration is the antagonistic relationship between the default mode network (encompassing mainly midline cortical regions) and frontoparietal areas (DMN anticorrelations). Functional anticorrelations especially have been shown to be important for behavior and consciousness, as they are absent or substantially reduced in early developmental stages, states of anesthesia, and disorders of consciousness. To date, though, theories of consciousness do not frame the anticorrelations in a comprehensive manner. Here, by tackling their biological origins, we suggest that neural inhibition is the underlying mechanism which mediates the emerging architecture of the fMRI anticorrelations. We go on to propose that neural inhibition reflects the process of functional segregation, namely the capacity of the brain to show selectivity in the areas which will be functionally connected. We then see how this view of segregation is met in the Global Neuronal Workspace Theory (GNWT, inhibition) and the Integrated Information Theory (IIT, differentiation) and propose that the anticorrelations can be considered as the quantifiable counterpart of these theoretical notions. We believe that this stance on functional anticorrelations will shed more light on what inter-network antagonism means for consciousness, and will open discussions about pragmatic quantifications of theoretical notions within consciousness research.


2020 ◽  
Vol 21 (11) ◽  
pp. 3975 ◽  
Author(s):  
Yasuko Honjo ◽  
Tatsuo Ichinohe

Early embryonic cells are sensitive to genotoxic stressors such as ionizing radiation. However, sensitivity to these stressors varies depending on the embryonic stage. Recently, the sensitivity and response to ionizing radiation were found to differ during the preimplantation period. The cellular and molecular mechanisms underlying the change during this period are beginning to be elucidated. In this review, we focus on the changes in radio-sensitivity and responses to ionizing radiation during the early developmental stages of the preimplantation (before gastrulation) period in mammals, Xenopus, and fish. Furthermore, we discuss the underlying cellular and molecular mechanisms and the similarities and differences between species.


2017 ◽  
Vol 114 (34) ◽  
pp. 9188-9193 ◽  
Author(s):  
Quan Lin ◽  
Ravikumar Ponnusamy ◽  
Jocelyn Widagdo ◽  
Jung A. Choi ◽  
Weihong Ge ◽  
...  

The prenatal period of cortical development is important for the establishment of neural circuitry and functional connectivity of the brain; however, the molecular mechanisms underlying this process remain unclear. Here we report that disruption of the actin–cytoskeletal network in the developing mouse prefrontal cortex alters dendritic morphogenesis and synapse formation, leading to enhanced formation of fear-related memory in adulthood. These effects are mediated by a brain-enriched microRNA, miR-9, through its negative regulation of diaphanous homologous protein 1 (Diap1), a key organizer of the actin cytoskeletal assembly. Our findings not only revealed important regulation of dendritogenesis and synaptogenesis during early brain development but also demonstrated a tight link between these early developmental events and cognitive functions later in life.


Author(s):  
J. P. Revel

Movement of individual cells or of cell sheets and complex patterns of folding play a prominent role in the early developmental stages of the embryo. Our understanding of these processes is based on three- dimensional reconstructions laboriously prepared from serial sections, and from autoradiographic and other studies. Many concepts have also evolved from extrapolation of investigations of cell movement carried out in vitro. The scanning electron microscope now allows us to examine some of these events in situ. It is possible to prepare dissections of embryos and even of tissues of adult animals which reveal existing relationships between various structures more readily than used to be possible vithout an SEM.


2017 ◽  
Vol 186 (1) ◽  
pp. 103-112
Author(s):  
Lukáš Laibl ◽  
Oldřich Fatka

This contribution briefly summarizes the history of research, modes of preservation and stratigraphic distribution of 51 trilobite and five agnostid taxa from the Barrandian area, for which the early developmental stages have been described.


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