The zebrafish udu gene encodes a novel nuclear factor and is essential for primitive erythroid cell development

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Yanmei Liu ◽  
Linsen Du ◽  
Motomi Osato ◽  
Eng Hui Teo ◽  
Feng Qian ◽  
...  
Keyword(s):  
Positional Cloning ◽  
Erythroid Cell ◽  
Nuclear Factor ◽  
Loss Of Function ◽  
Cell Proliferation And Differentiation ◽  
Complex Process ◽  
Proliferation And Differentiation ◽  
Ugly Duckling ◽  
A Cell ◽  
Α Helix

Hematopoiesis is a complex process which gives rise to all blood lineages in the course of an organism's lifespan. However, the underlying molecular mechanism governing this process is not fully understood. Here we report the isolation and detailed study of a newly identified zebrafish ugly duckling (Udu) mutant allele, Udusq1. We show that loss-of-function mutation in the udu gene disrupts primitive erythroid cell proliferation and differentiation in a cell-autonomous manner, resulting in red blood cell (RBC) hypoplasia. Positional cloning reveals that the Udu gene encodes a novel factor that contains 2 paired amphipathic α-helix–like (PAH-L) repeats and a putative SANT-L (SW13, ADA2, N-Cor, and TFIIIB–like) domain. We further show that the Udu protein is predominantly localized in the nucleus and deletion of the putative SANT-L domain abolishes its function. Our study indicates that the Udu protein is very likely to function as a transcription modulator essential for the proliferation and differentiation of erythroid lineage.

Cell-intrinsic requirement for pRb in erythropoiesis

Blood ◽  
2004 ◽  
Vol 104 (5) ◽  
pp. 1324-1326 ◽  
Author(s):  
Allison J. Clark ◽  
Kathryn M. Doyle ◽  
Patrick O. Humbert
Keyword(s):  
Erythroid Differentiation ◽  
Published Data ◽  
Erythroid Cells ◽  
Cell Cycle Exit ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
A Cell ◽  
Rb Gene

Abstract Retinoblastoma (Rb) and family members have been implicated as key regulators of cell proliferation and differentiation. In particular, accumulated data have suggested that the Rb gene product pRb is an important controller of erythroid differentiation. However, current published data are conflicting as to whether the role of pRb in erythroid cells is cell intrinsic or non–cell intrinsic. Here, we have made use of an in vitro erythroid differentiation culture system to determine the cell-intrinsic requirement for pRb in erythroid differentiation. We demonstrate that the loss of pRb function in primary differentiating erythroid cells results in impaired cell cycle exit and terminal differentiation. Furthermore, we have used coculture experiments to establish that this requirement is cell intrinsic. Together, these data unequivocally demonstrate that pRb is required in a cell-intrinsic manner for erythroid differentiation and provide clarification as to its role in erythropoiesis.

A Systematic Screen for Dominant Second-Site Modifiers of Merlin/NF2 Phenotypes Reveals an Interaction With blistered/DSRF and scribbler

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 667-679
Author(s):  
Dennis R LaJeunesse ◽  
Brooke M McCartney ◽  
Richard G Fehon
Keyword(s):  
Human Tumor ◽  
Suppressor Gene ◽  
Dominant Negative ◽  
Loss Of Function ◽  
Genetic Screens ◽  
Cellular Functions ◽  
Cell Proliferation And Differentiation ◽  
Epithelial Development ◽  
Proliferation And Differentiation ◽  
Neuronal Tissues

Abstract Merlin, the Drosophila homologue of the human tumor suppressor gene Neurofibromatosis 2 (NF2), is required for the regulation of cell proliferation and differentiation. To better understand the cellular functions of the NF2 gene product, Merlin, recent work has concentrated on identifying proteins with which it interacts either physically or functionally. In this article, we describe genetic screens designed to isolate second-site modifiers of Merlin phenotypes from which we have identified five multiallelic complementation groups that modify both loss-of-function and dominant-negative Merlin phenotypes. Three of these groups, Group IIa/scribbler (also known as brakeless), Group IIc/blistered, and Group IId/net, are known genes, while two appear to be novel. In addition, two genes, Group IIa/scribbler and Group IIc/blistered, alter Merlin subcellular localization in epithelial and neuronal tissues, suggesting that they regulate Merlin trafficking or function. Furthermore, we show that mutations in scribbler and blistered display second-site noncomplementation with one another. These results suggest that Merlin, blistered, and scribbler function together in a common pathway to regulate Drosophila wing epithelial development.

scholarly journals Au, Pd and maghemite nanofunctionalized hydroxyapatite scaffolds for bone regeneration

2020 ◽  
Vol 7 (5) ◽  
pp. 461-469
Author(s):  
Giovanna Calabrese ◽  
Salvatore Petralia ◽  
Claudia Fabbi ◽  
Stefano Forte ◽  
Domenico Franco ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Gold Nanorods ◽  
Type I ◽  
Maghemite Nanoparticles ◽  
Cell Growth Inhibition ◽  
Cytotoxic Effects ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
A Cell ◽  
Calcium Deposits

Abstract Nanotechnology plays a key role in the development of innovative scaffolds for bone tissue engineering (BTE) allowing the incorporation of nanomaterials able to improve cell proliferation and differentiation. In this study, Mg-HA-Coll type I scaffolds (Mg-HA-based scaffolds) were nanofunctionalized with gold nanorods (Au NRs), palladium nanoparticles (Pd NPs) and maghemite nanoparticles (MAG NPs). Nanofunctionalized Mg-HA-based scaffolds (NF-HA-Ss) were tested for their ability to promote both the proliferation and the differentiation of adipose-derived mesenchymal stem cells (hADSCs). Results clearly highlight that MAG nanofunctionalization substantially improves cell proliferation up to 70% compared with the control (Mg-HA-based scaffold), whereas both Au NRs and Pd NPs nanofunctionalization induce a cell growth inhibition of 94% and 89%, respectively. Similar evidences were found for the osteoinductive properties showing relevant calcium deposits (25% higher than the control) for MAG nanofunctionalization, while a decreasing of cell differentiation (20% lower than the control) for both Au NRs and Pd NPs derivatization. These results are in agreement with previous studies that found cytotoxic effects for both Pd NPs and Au NRs. The excellent improvement of both osteoconductivity and osteoinductivity of the MAG NF-HA-S could be attributed to the high intrinsic magnetic field of superparamagnetic MAG NPs. These findings may pave the way for the development of innovative nanostructured scaffolds for BTE.

scholarly journals Quantitatively Controlled Fabrication of Uniaxially Aligned Nanofibrous Scaffold for Cell Adhesion

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Suk Hee Park ◽  
Jung Woo Hong ◽  
Jennifer Hyunjong Shin ◽  
Dong-Yol Yang
Keyword(s):  
Electrospinning Process ◽  
Dermal Fibroblasts ◽  
Fiber Formation ◽  
Actin Stress Fiber ◽  
Promote Cell Proliferation ◽  
Nanofiber Scaffold ◽  
Cell Proliferation And Differentiation ◽  
Fiber Spacing ◽  
Proliferation And Differentiation ◽  
A Cell

In light of tissue engineering, development of a functional and controllable scaffold which can promote cell proliferation and differentiation is crucial. In this study, we introduce a controllable collection method of the electrospinning process for regularly-distributed and uniaxially oriented nanofiber scaffold and evaluate the effects of aligned nanofiber density on adhesion of dermal fibroblasts. The suggested spinning collector features an inclined void gap, which allows easy transfer of uniformly aligned fibers onto other surfaces. By undergoing multiple transfers, the density of the nanofibers can be quantitatively controlled. The resultant polycaprolactone (PCL) nanofibers had well-defined nanotopography in a 400–600 nm range. Human dermal fibroblasts were seeded on aligned nanofiber scaffolds of different densities achieved by varying the number of transfers. Cell morphology and actin stress fiber formation was accessed after seven days. The experimental results indicate that the contact guidance of the cells along the fiber alignment can be more activated with more than one guidance feature on a cell; that is, the high density of fiber is attained in so much that fiber spacing gets below the cell size.

scholarly journals Targeting of SET/I2PP2A oncoprotein inhibits Gli1 transcription revealing a new modulator of Hedgehog signaling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iliana Serifi ◽  
Simoni Besta ◽  
Zoe Karetsou ◽  
Panagiota Giardoglou ◽  
Dimitris Beis ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Hedgehog Signaling ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Patterning Defect ◽  
Hh Signaling ◽  
Expression In Mammalian Cells

AbstractThe Hedgehog (Hh)/Gli signaling pathway controls cell proliferation and differentiation, is critical for the development of nearly every tissue and organ in vertebrates and is also involved in tumorigenesis. In this study, we characterize the oncoprotein SET/I2PP2A as a novel regulator of Hh signaling. Our previous work has shown that the zebrafish homologs of SET are expressed during early development and localized in the ciliated organs. In the present work, we show that CRISPR/Cas9-mediated knockdown of setb gene in zebrafish embryos resulted in cyclopia, a characteristic patterning defect previously reported in Hh mutants. Consistent with these findings, targeting setb gene using CRISPR/Cas9 or a setb morpholino, reduced Gli1-dependent mCherry expression in the Hedgehog reporter zebrafish line Tg(12xGliBS:mCherry-NLS). Likewise, SET loss of function by means of pharmacological inhibition and gene knockdown prevented the increase of Gli1 expression in mammalian cells in vitro. Conversely, overexpression of SET resulted in an increase of the expression of a Gli-dependent luciferase reporter, an effect likely attributable to the relief of the Sufu-mediated inhibition of Gli1. Collectively, our data support the involvement of SET in Gli1-mediated transcription and suggest the oncoprotein SET/I2PP2A as a new modulator of Hedgehog signaling.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

Icariin Stimulates hFOB 1.19 Osteoblast Proliferation and Differentiation via OPG/RANKL Mediated by the Estrogen Receptor

2020 ◽  
Vol 22 (1) ◽  
pp. 168-175 ◽  
Author(s):  
Lin-Jun Sun ◽  
Chong Li ◽  
Xiang-hao Wen ◽  
Lu Guo ◽  
Zi-Fen Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Protein Expression ◽  
Chinese Herb ◽  
Human Osteoblast ◽  
Osteoblast Cells ◽  
Expression Ratio ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mrna And Protein Expression

Background:: Icariin (ICA), one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis. Methods:: Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in hFOB1.19 human osteoblast cells. Results:: The experimental results show that ICA can stimulate cell proliferation and increase the activity of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/ RANKL mRNA and protein expression ratios were upregulated by ICA. The above-mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of the upregulated expression is connected with the estrogen receptor. In conclusion, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.

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