scholarly journals Non-apoptotic enteroblast-specific role of the initiator caspase Dronc for development and homeostasis of the Drosophila intestine

2020 ◽  
Author(s):  
Jillian L. Lindblad ◽  
Meghana Tare ◽  
Alla Amcheslavsky ◽  
Alicia Shields ◽  
Andreas Bergmann
Keyword(s):  
Normal Development ◽  
Cell Lineage ◽  
Cell Types ◽  
List Type ◽  
Apoptotic Pathway ◽  
Specific Expression ◽  
Critical Function ◽  
Card Domain ◽  
Proliferation And Differentiation

SummaryThe initiator caspase Dronc is the only CARD-domain containing caspase in Drosophila and is essential for apoptosis. Here, we report that homozygous dronc mutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression of dronc+ in dronc mutant animals, suggesting that proper Drone function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown of dronc in adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Drone do not require the apoptotic pathway and thus occur in a non-apoptotic manner. In summary, we demonstrate that an apoptotic initiator caspase has a very critical non-apoptotic function for normal development and for the control of the cell lineage in the adult midgut and therefore for proper physiology and homeostasis.Highlightsdronc mutants die from a fragile and leaky intestinedronc has a critical function in enteroblasts of the intestinedronc controls proliferation and differentiation in the intestinedronc performs these functions in an apoptosis-independent (non-apoptotic) manner

scholarly journals Non-apoptotic enteroblast-specific role of the initiator caspase Dronc for development and homeostasis of the Drosophila intestine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jillian L. Lindblad ◽  
Meghana Tare ◽  
Alla Amcheslavsky ◽  
Alicia Shields ◽  
Andreas Bergmann
Keyword(s):  
Normal Development ◽  
Cell Lineage ◽  
Cell Types ◽  
Specific Role ◽  
Mutant Phenotype ◽  
Apoptotic Pathway ◽  
Specific Expression ◽  
Card Domain

AbstractThe initiator caspase Dronc is the only CARD-domain containing caspase in Drosophila and is essential for apoptosis. Here, we report that homozygous dronc mutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression of dronc+ in dronc mutant animals, suggesting that proper Dronc function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown of dronc in adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Dronc do not require the apoptotic pathway and thus occur in a non-apoptotic manner. In summary, we demonstrate that an apoptotic initiator caspase has a very critical non-apoptotic function for normal development and for the control of the cell lineage in the adult midgut and therefore for proper physiology and homeostasis.

scholarly journals An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 409-429
Author(s):  
Matthew B. Lohse ◽  
Lucas R. Brenes ◽  
Naomi Ziv ◽  
Michael B. Winter ◽  
Charles S. Craik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Specific Expression ◽  
Environmental Signals ◽  
Single Genome ◽  
Distinct Cell ◽  
Secreted Proteases ◽  
Expression Program

An unusual feature of the opportunistic pathogen Candida albicans is its ability to switch stochastically between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively upregulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases [members of the secreted aspartyl protease (SAP) family] needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.

Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney

2000 ◽  
Vol 278 (5) ◽  
pp. F737-F746 ◽  
Author(s):  
Vanishree Murthy ◽  
Luciana A. Haddad ◽  
Nicole Smith ◽  
Denise Pinney ◽  
Robert Tyszkowski ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Cell Types ◽  
Intercalated Cells ◽  
Autosomal Dominant Disorder ◽  
Specific Expression ◽  
Multiple Organs ◽  
Distal Tubules ◽  
Kidney Lesions ◽  
The Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs, notably the brain and kidneys. The disease is caused by mutations in TSC1or TSC2 genes, coding hamartin and tuberin, respectively. Immunofluorescence analysis of tuberin and hamartin performed here demonstrates that both proteins are specifically expressed in the distal urinary tubule, comprising the distal tubules, connecting segment, and collecting ducts. Hamartin, distinct from tuberin, is expressed in the thick ascending limbs of Henle and in juxtaglomerular cells, where it colocalizes with renin. In positive epithelial cells, tuberin localizes to the cytoplasm as well as the apical membrane. Hamartin, however, preferentially localizes to the apical membrane. The two proteins colocalize at the apical membrane of type A intercalated cells and connecting tubule cells, whereas in type B intercalated cells they reveal a variable pattern of expression. The cell-specific expression of tuberin and hamartin described here will provide critical insight into the cell types that give rise to kidney lesions, and the tumor suppressor role of these proteins in TSC.

scholarly journals Regulation of the fructose transporter GLUT5 in health and disease

2008 ◽  
Vol 295 (2) ◽  
pp. E227-E237 ◽  
Author(s):  
Veronique Douard ◽  
Ronaldo P. Ferraris
Keyword(s):  
Normal Development ◽  
Cell Types ◽  
Mammary Glands ◽  
Fat Tissue ◽  
Metabolic Disturbances ◽  
Research Areas ◽  
Yield Information ◽  
Uptake Rates ◽  
Health And Disease

Fructose is now such an important component of human diets that increasing attention is being focused on the fructose transporter GLUT5. In this review, we describe the regulation of GLUT5 not only in the intestine and testis, where it was first discovered, but also in the kidney, skeletal muscle, fat tissue, and brain where increasing numbers of cell types have been found to have GLUT5. GLUT5 expression levels and fructose uptake rates are also significantly affected by diabetes, hypertension, obesity, and inflammation and seem to be induced during carcinogenesis, particularly in the mammary glands. We end by highlighting research areas that should yield information needed to better understand the role of GLUT5 during normal development, metabolic disturbances, and cancer.

scholarly journals Astrocyte-like glia-specific gene deathstar is crucial for normal development, adult locomotion and lifespan of male Drosophila

2019 ◽  
Author(s):  
Hadi Najafi ◽  
Kyle Wong ◽  
Woo Jae Kim
Keyword(s):  
Nervous System ◽  
Expression Pattern ◽  
Normal Development ◽  
Optic Lobe ◽  
Cell Types ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Bioinformatical Analysis ◽  
Specific Expression Pattern

ABSTRACTDrosophila melanogaster is a proper model organism for studying the development and function of the nervous system. The Drosophila nervous system consists of distinct cell types with significant homologies to various cell types of more advanced organisms, including human. Among all cell types of the nervous system, astrocyte-like glia (ALG) have conserved functions to mammals and are essential for normal physiology and behaviours of the fly.In this study, we exploited the gene expression profile of single cells in Drosophila optic lobe to identify the genes with specific expression pattern in each cell type. Through a bioinformatical analysis of the data, a novel ALG-specific gene (here assigned as deathstar) was identified. Immunostaining of deathstar in the central nervous system (CNS) showed its presence in specific regions of Drosophila ventral nerve cord, which previously has been characterized as ALG cells. Consistent with the bioinformatical analysis, deathstar-related signals were overlapped with the signals of the previously-reported ALG marker, Eaat1, supporting its specific expression in ALG cells.At the physiological level, RNAi-mediated suppression of deathstar gene impeded the normal development of male flies without any effects on females. Cell type-specific expression of deathstar RNAi showed that deathstar gene affects locomotion behaviour and lifespan of D. melanogaster, in an ALG-specific manner.Taken together, we showed that bioinformatical analysis of a previously reported expression data of Drosophila optic lobe successfully predicted the ALG-specific expression pattern of deathstar gene. Moreover, it was consistent with the ALG-specific effects of this gene on locomotion and lifespan of D. melanogaster, in vivo.

scholarly journals Epidermal CFTR Suppresses MAPK/NF-κB to Promote Cutaneous Wound Healing

2016 ◽  
Vol 39 (6) ◽  
pp. 2262-2274 ◽  
Author(s):  
Jing Chen ◽  
Yu Chen ◽  
Yajie Chen ◽  
Zicheng Yang ◽  
Bo You ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Types ◽  
Hacat Cells ◽  
Cutaneous Wound Healing ◽  
Keratinocyte Proliferation ◽  
Cutaneous Wound ◽  
Human Keratinocyte ◽  
Proliferation And Differentiation ◽  
Underlying Mechanisms

Background: CFTR is implicated in cutaneous wound healing although the underlying mechanisms are not fully understood. In other cell types, CFTR is reported to regulate MAPK/ NF-κB signaling. We undertook the present study to explore a possible role of CFTR in regulating MAPK/NF-κB during cutaneous wound healing. Methods& Results: The splint-excisional and incisional wound healing models were used in CFTR mutant (DF508) mice. The cell-scratch model was used in a human keratinocyte line, HaCaT, in conjunction with CFTR knockdown or overexpression. The epidermal inflammation, keratinocyte proliferation and differentiation, as well as MAPK/NF-κB signaling were examined. Inhibitors of MAPK/NF-κB were also used. Results: Both DF508 mice and HaCaT cells with CFTR knockdown exhibited delayed cutaneous wound healing with exuberant inflammation, increased proliferation and aberrant differentiation. Knockdown of CFTR in HaCaT cells resulted in phosphorylation of ERK, p38 and IκBα. The disturbance of inflammation, proliferation and differentiation in HaCaT cells were reversed by CFTR overexpression or inhibition of MAPK or NF-κB. Conclusion: CFTR plays a role in suppressing MAPK/NF-κB to relieve inflammation, reduce proliferation and promote differentiation of keratinocytes, and thus promotes cutaneous wound healing.

scholarly journals Neuronal Developmental Marker FORSE-1 Identifies a Putative Progenitor of the Pulmonary Neuroendocrine Cell Lineage During Lung Development

2002 ◽  
Vol 50 (12) ◽  
pp. 1567-1578 ◽  
Author(s):  
Jie Pan ◽  
Herman Yeger ◽  
Ernest Cutz
Keyword(s):  
Lung Development ◽  
Early Stage ◽  
Cell Lineage ◽  
Antigen Expression ◽  
Cell Types ◽  
Cell System ◽  
Neuroendocrine Cells ◽  
Tissue Sections ◽  
Brdu Labeling

The FORSE-1 ( forebrain-surface-embryonic) monoclonal antibody (MAb) recognizes a carbohydrate cell surface epitope related to the Lewis-X (LeX) and stage-specific embryonic antigens (SSEAs). In the developing CNS, the FORSE-1 epitope is believed to serve as a marker of progenitor cells. We studied the expression of the FORSE-1 epitope in pulmonary neuroendocrine cells (PNECs) and related neuroepithelial bodies (NEBs), cell types implicated in paracrine regulation of lung development. We used dual immunolabeling to identify PNECs/NEBs in tissue sections from developing rabbit fetal lungs and corresponding primary lung cell cultures. During the early stage (E16), the FORSE-1 MAb labeled primitive airway epithelium, whereas serotonin (5HT) immunoreactivity, a marker of PNEC/NEB differentiation, was negative. After E18, FORSE-1 labeling became restricted to PNECs and NEBs, identified by co-expression with 5HT, then decreased coincident with an increase in 5HT. Expression of the FORSE-1 epitope correlated inversely with 5HT expression in PNEC/NEB cells. FORSE-1 immunoreactivity correlated with cell proliferation assessed by BrdU labeling. Downregulation of the FORSE-1 epitope correlated with maturation of PNECs/NEBs. The presence of few FORSE-1/5HT-positive cells in postnatal lung suggests retention of progenitors. The FORSE-1 epitope was associated with a high molecular weight (286 kD) glycoprotein that decreased with increasing gestational age, as demonstrated by immunoblotting. Overall expression of SSEA-1, −3, and −4 antigens was similar to FORSE-1/5HT, although the former was preferentially localized to neurite-like processes. Because the role of the FORSE-1 epitope in the CNS probably involves cell adhesion and differentiation, we propose a similar function in developing lung. The demonstration of LeX/SSEA antigen expression in the PNEC/NEB cell lineage underscores the importance of these cells in developing lung. Furthermore, the FORSE-1 antigen may identify committed progenitors of the PNEC/NEB cell system.

scholarly journals Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues.

1990 ◽  
Vol 110 (3) ◽  
pp. 753-765 ◽  
Author(s):  
A M Gonzalez ◽  
M Buscaglia ◽  
M Ong ◽  
A Baird
Keyword(s):  
Cell Types ◽  
Wide Distribution ◽  
Basement Membranes ◽  
Specific Staining ◽  
Rat Fetus ◽  
Basic Fgf ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Cell Growth And Differentiation

Immunohistochemical methods were used to study the distribution of basic FGF in the 18-d rat fetus. The results reveal a pattern of widespread yet specific staining that is consistent with the wide distribution of basic FGF. Immunoreactive basic FGF is associated with mesenchymal structures, mesoderm- and neuroectoderm-derived cells, and their extracellular matrices. As an example, skeletal and smooth muscle cells are strongly positive. The basement membrane underlying the epithelia always contain basic FGF. In some tissues (i.e., cartilage and bone) the intensity of immunostaining is dependent on the stage of cell differentiation. Although the staining of tissues is primarily associated with the extracellular matrix, there is significant intracellular staining in various cell types. This is particularly evident in the endocrine cells of the adrenal cortex, testis, and ovary. The histochemical findings reported here support the notion that basic FGF has the characteristics required to mediate many of the effects of the mesenchyme on cell growth and differentiation. The significance of these findings in understanding the role of basic FGF in regulating cell proliferation and differentiation is discussed.

scholarly journals In Search of Molecular Markers for Cerebellar Neurons

2021 ◽  
Vol 22 (4) ◽  
pp. 1850
Author(s):  
Wing Yip Tam ◽  
Xia Wang ◽  
Andy S. K. Cheng ◽  
Kwok-Kuen Cheung
Keyword(s):  
Cognitive Deficits ◽  
Motor Coordination ◽  
Normal Development ◽  
Genetic Manipulation ◽  
Cell Types ◽  
Functional Study ◽  
Cerebellar Neurons ◽  
The Brain ◽  
Neuronal Type

The cerebellum, the region of the brain primarily responsible for motor coordination and balance, also contributes to non-motor functions, such as cognition, speech, and language comprehension. Maldevelopment and dysfunction of the cerebellum lead to cerebellar ataxia and may even be associated with autism, depression, and cognitive deficits. Hence, normal development of the cerebellum and its neuronal circuitry is critical for the cerebellum to function properly. Although nine major types of cerebellar neurons have been identified in the cerebellar cortex to date, the exact functions of each type are not fully understood due to a lack of cell-specific markers in neurons that renders cell-specific labeling and functional study by genetic manipulation unfeasible. The availability of cell-specific markers is thus vital for understanding the role of each neuronal type in the cerebellum and for elucidating the interactions between cell types within both the developing and mature cerebellum. This review discusses various technical approaches and recent progress in the search for cell-specific markers for cerebellar neurons.

scholarly journals Ligand-Independent Antiapoptotic Function of Estrogen Receptor-β in Lung Cancer Cells

2010 ◽  
Vol 24 (9) ◽  
pp. 1737-1747 ◽  
Author(s):  
GuangFeng Zhang ◽  
Naveena Yanamala ◽  
Kira L. Lathrop ◽  
Lin Zhang ◽  
Judith Klein-Seetharaman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Estrogen Receptor ◽  
Cell Types ◽  
Mitochondrial Fraction ◽  
Apoptotic Pathway ◽  
Independent Manner ◽  
Bh3 Domain ◽  
Exact Function ◽  
Apoptosis Inducing Agents

Abstract Recent studies have demonstrated the presence of estrogen receptor (ER)β in the mitochondria in various cell types and tissues, but the exact function of this localization remains unclear. In this study, we have examined the function of mitochondrial ERβ in non-small-cell lung cancer (NSCLC) cells. Down-regulation of ERβ by short hairpin RNA constructs sensitized NSCLC cells to various apoptosis-inducing agents such as cisplatin, taxol, and etoposide. The increased growth inhibition and induction of apoptosis in ERβ-knockdown cells was observed irrespective of estrogen treatment, suggesting a ligand-independent role of ERβ in regulating the intrinsic apoptotic pathway. Further, ERβ from the mitochondrial fraction physically interacted with the proapoptotic protein Bad, in a ligand-independent manner. Glutathione-S-transferase pull-down assays and molecular modeling studies revealed that the DNA-binding domain and hinge region of ERβ, and the BH3 domain of Bad were involved in these interactions. Further investigations revealed that ERβ inhibited Bad function by disrupting Bad-Bcl-XL and Bad-Bcl-2 interactions. Reintroduction of ERβ in the mitochondria of ERβ knockdown cells reversed their sensitivity to cisplatin. Overall, our results demonstrate a ligand-independent role of ERβ in regulating apoptosis, revealing a novel function for ERβ in the mitochondria.

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