Transcriptional regulation of Notch and Delta: requirement for neuroblast segregation in Drosophila

Development ◽  
1997 ◽  
Vol 124 (10) ◽  
pp. 2015-2025 ◽  
Author(s):  
L. Seugnet ◽  
P. Simpson ◽  
M. Haenlin

Segregation of a single neural precursor from each proneural cluster in Drosophila relies on Notch-mediated lateral signalling. Studies concerning the spacing of precursors for the microchaetes of the peripheral nervous system suggested the existence of a regulatory loop between Notch and its ligand Delta within each cell that is under transcriptional control. Activation of Notch leads to repression of the achaete-scute genes which themselves regulate transcription of Delta, perhaps directly. Here we have tested a requirement for transcriptional regulation of Notch and/or Delta during neuroblast segregation in embryos, by providing Notch and Delta ubiquitously at uniform levels. Neuroblast segregation occurs normally under conditions of uniform Notch expression. Under conditions of uniform Delta expression, a single neuroblast segregates from each proneural group in 80% of the cases, more than one in the remaining 20%. Thus transcriptional regulation of Delta is largely dispensable. We discuss the possibility that segregation of single precursors in the central nervous system may rely on a heterogeneous distribution of neural potential between different cells of the proneural group. Notch signalling would enable all cells to mutually repress each other and only a cell with an elevated neural potential could overcome this repression.

Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 927-932 ◽  
Author(s):  
P. Simpson ◽  
C. Carteret

The segregation of neural precursors from epidermal cells during development of the nervous system of Drosophila relies on interactions between cells that are thought to be initially equivalent. During development of the adult peripheral nervous system, failure of the cellular interactions leads to the differentiation of a tuft of sensory bristles at the site where usually only one develops. It is thus thought that a group of cells at that site (a proneural cluster) has the potential to make a bristle but that in normal development only one cell will do so. The question addressed here is do these cells constitute an equivalence group (Kimble, J., Sulston, J. and White, J. (1979). In Cell Lineage, Stem Cells and Cell Determination (ed. N. Le Douarin). Inserm Symposium No. 10 pp. 59–68, Elsevier, Amsterdam)? Within clusters mutant for shaggy, where several cells of a cluster follow the neural fate and differentiate bristles, it is shown that these display identical neuronal specificity: stimulation of the bristles evoke the same leg cleaning response and backfilling of single neurons reveal similar axonal projections in the central nervous system. This provides direct experimental evidence that the cells of a proneural cluster are developmentally equivalent.


2018 ◽  
Vol 35 (11) ◽  
pp. 1100-1106
Author(s):  
Alexa Calero ◽  
Hazel Villanueva ◽  
Priyadarshani Giri ◽  
Arthur Tischler ◽  
James Powers ◽  
...  

Objective Prior to maturation of the human sympathetic nervous system, the neonatal adrenal medulla senses and responds to hypoxia. In addition to catecholamine release, the adrenal medulla synthesizes and stores opioid peptides, notably enkephalin (ENK). However, it is not known whether acute hypoxia evokes adrenal ENK production and release, as seen in the central nervous system (CNS). We hypothesize that acute hypoxia stimulates synthesis and release of ENK in chromaffin cells. Study Design Cultures of adrenergic mouse pheochromocytoma cells (MPC) 10/9/96CR were incubated in 10% oxygen (O2) at intervals of up to 60 minutes. ENK content and release were measured by Met-ENK enzyme-linked immunosorbent assay (ELISA). ENK messenger ribonucleic acid (mRNA) was analyzed by quantitative reverse-transcriptase polymerase chain reaction (PCR). Results Incubation of MPC 10/9 cells in 10% O2 evoked rapid release of epinephrine and of Met-ENK which increased approximately twofold in 15 minutes. Reduced [O2] also induced an overall increase (14%) in cellular ENK peptide content within 60 minutes. Acute hypoxia-stimulated release of Met-ENK was accompanied by increased mRNAENK expression in MPC 10/9s, a cell culture model of adrenergic chromaffin cells. Conclusion We speculate that the ability of reduced [O2] to evoke ENK release from chromaffin cells may influence blood pressure regulation and heart contractility, thereby providing an adaptive survival advantage during neonatal asphyxia.


2020 ◽  
Author(s):  
Ting-Ting Luo ◽  
Chun-Qiu Dai ◽  
Jia-Qi Wang ◽  
Zheng-Mei Wang ◽  
Yi Yang ◽  
...  

Abstract Objectives: Drp1 is widely expressed in the mouse central nervous system and plays a role in inducing the mitochondrial fission process. Many diseases are associated with Drp1 and mitochondria. However, since the exact distribution of Drp1 has not been specifically observed, it is difficult to determine the impact of anti-Drp1 molecules on the human body. Clarifying the specific Drp1 distribution could be a good approach to targeted treatment or prognosis. Methods: We visualized the distribution of Drp1 in different brain regions and explicated the relationship between Drp1 and mitochondria. GAD67-GFP knock-in mice were utilized to detect the expression patterns of Drp1 in GABAergic neurons. We also further analyzed Drp1 expression in human malignant glioma tissue. Results : Drp1 was widely but heterogeneously distributed in the central nervous system. Further observation indicated that Drp1 was highly and heterogeneously expressed in inhibitory neurons. Under transmission electron microscopy, the distribution of Drp1 was higher in dendrites than other areas in neurons, and only a small amount of Drp1 was localized in mitochondria. In human malignant glioma, the fluorescence intensity of Drp1 increased from grade I-III, while grade IV showed a declining trend. Conclusion: In this study, we observed a wide heterogeneous distribution of Drp1 in the central nervous system, which might be related to the occurrence and development of neurologic disease. We hope that the relationship between Drp1 and mitochondria may will to therapeutic guidance in the clinic.


Development ◽  
1989 ◽  
Vol 107 (4) ◽  
pp. 855-862 ◽  
Author(s):  
S. Tix ◽  
M. Bate ◽  
G.M. Technau

Injection of a cell lineage tracer (HRP) into Drosophila embryos before cellularization provides a way of selectively labelling cells at later stages that have undergone only a few mitoses. All cells born and differentiating during embryogenesis become labelled, whereas further proliferation and growth during postembryonic development causes an almost complete dilution of the marker in the adult cell complement. Early born neurons visualized in this way are good candidates for executing a pioneering function during postembryonic differentiation of the adult nervous system. In all three pairs of leg imaginal discs, a stereotyped set of larval sense organs becomes selectively labelled. Their axons fasciculate with a larval nerve, which connects the leg disc with the central nervous system. Larval sense organs are not present in the other imaginal discs. Larval neurons are not present in the transformed antennal discs of Antp 73B flies. Nonetheless adult axons successfully navigate to the base of these discs as they differentiate to form ectopic legs. We conclude that embryonically formed larval nerves are not essential for the guidance of adult axons within the leg discs.


2015 ◽  
Vol 90 (5) ◽  
pp. 2600-2615 ◽  
Author(s):  
Tiffany M. Lucas ◽  
Justin M. Richner ◽  
Michael S. Diamond

ABSTRACTThe mammalian host responds to viral infections by inducing expression of hundreds of interferon-stimulated genes (ISGs). While the functional significance of many ISGs has yet to be determined, their cell type and temporal nature of expression suggest unique activities against specific pathogens. Using a combination of ectopic expression and gene silencing approaches in cell culture, we previously identifiedIfi27l2aas a candidate antiviral ISG within neuronal subsets of the central nervous system (CNS) that restricts infection by West Nile virus (WNV), an encephalitic flavivirus of global concern. To investigate the physiological relevance of Ifi27l2a in the context of viral infection, we generatedIfi27l2a−/−mice. Although adult mice lackingIfi27l2awere more vulnerable to lethal WNV infection, the viral burden was greater only within the CNS, particularly in the brain stem, cerebellum, and spinal cord. Within neurons of the cerebellum and brain stem, in the context of WNV infection, a deficiency of Ifi27l2a was associated with less cell death, which likely contributed to sustained viral replication and higher titers in these regions. Infection studies in a primary cell culture revealed thatIfi27l2a−/−cerebellar granule cell neurons and macrophages but not cerebral cortical neurons, embryonic fibroblasts, or dendritic cells sustained higher levels of WNV infection than wild-type cells and that this difference was greater under conditions of beta interferon (IFN-β) pretreatment. Collectively, these findings suggest that Ifi27l2a has an antiviral phenotype in subsets of cells and that at least some ISGs have specific inhibitory functions in restricted tissues.IMPORTANCEThe interferon-stimulatedIfi27l2agene is expressed differentially within the central nervous system upon interferon stimulation or viral infection. Prior studies in cell culture suggested an antiviral role for Ifi27l2a during infection by West Nile virus (WNV). To characterize its antiviral activityin vivo, we generated mice with a targeted gene deletion ofIfi27l2a. Based on extensive virological analyses, we determined that Ifi27l2a protects mice from WNV-induced mortality by contributing to the control of infection of the hindbrain and spinal cord, possibly by regulating cell death of neurons. This antiviral activity was validated in granule cell neurons derived from the cerebellum and in macrophages but was not observed in other cell types. Collectively, these data suggest that Ifi27l2a contributes to innate immune restriction of WNV in a cell-type- and tissue-specific manner.


1960 ◽  
Vol 8 (2) ◽  
pp. 431-446 ◽  
Author(s):  
A. Peters

The development and structure of myelin sheaths have been studied in the optic nerves of rats and of Xenopus laevis tadpoles. Both potassium permanganate- and osmium-fixed material was examined with the electron microscope. In the first stage of myelinogenesis the nerve fibre is surrounded by a cell process which envelops it and forms a mesaxon. The mesaxon then elongates into a loose spiral from which the cytoplasm is later excluded, so that compact myelin is formed. This process is similar to myelinogenesis in the peripheral nervous system, although in central fibres the cytoplasm on the outside of the myelin is confined in a tongue-like process to a fraction of the circumference, leaving the remainder of the sheath uncovered, so that contacts are possible between adjacent myelin sheaths. The structure of nodes in the central nervous system has been described and it is suggested that the oligodendrocytes may be the myelin-forming cells.


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