The Drosophila neurogenic gene big brain, which encodes a membrane-associated protein, acts cell autonomously and can act synergistically with Notch and Delta

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3881-3893 ◽  
Author(s):  
D. Doherty ◽  
L.Y. Jan ◽  
Y.N. Jan
Keyword(s):  
Cell Fate ◽  
Epidermal Cell ◽  
Neural Development ◽  
Gene Function ◽  
Sequence Similarity ◽  
Notch Pathway ◽  
Cell Communication ◽  
Communication Process ◽  
Neurogenic Genes ◽  
Proneural Cluster

In the developing nervous system of Drosophila, cells in each proneural cluster choose between neural and epidermal cell fates. The neurogenic genes mediate the cell-cell communication process whereby one cell adopts the neural cell fate and prevents other cells in the cluster from becoming neural. In the absence of neurogenic gene function, most, if not all of the cells become neural. big brain is a neurogenic gene that encodes a protein with sequence similarity to known channel proteins. It is unique among the neurogenic genes in that previous genetic studies have not revealed any interaction between big brain and the other neurogenic genes. Furthermore, the neural hypertrophy in big brain mutant embryos is less severe than that in embryos mutant for other neurogenic genes. In this paper, we show by antibody staining that bib is expressed in tissues that give rise to neural precursors and in other tissues that are affected by loss of neurogenic gene function. By immunoelectron microscopy, we found that bib is associated with the plasma membrane and concentrated in apical adherens junctions as well as in small cytoplasmic vesicles. Using mosaic analysis in the adult, we demonstrate that big brain activity is required autonomously in epidermal precursors to prevent neural development. Finally, we demonstrate that ectopically expressed big brain acts synergistically with ectopically expressed Delta and Notch, providing the first evidence that big brain may function by augmenting the activity of the Delta-Notch pathway. These results are consistent with bib acting as a channel protein in proneural cluster cells that adopt the epidermal cell fate, and serving a necessary function in the response of these cells to the lateral inhibition signal.

Influence of Drosophila ventral epidermal development by the CNS midline cells and spitz class genes

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 893-901 ◽  
Author(s):  
S.H. Kim ◽  
S.T. Crews
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Cell Fate ◽  
Epidermal Cell ◽  
Gene Function ◽  
Gene Expression Analysis ◽  
Cns Midline ◽  
Midline Cells ◽  
Enhancer Trap Lines ◽  
Epidermal Development

The ventral epidermis of Drosophila melanogaster is derived from longitudinal rows of ectodermal precursor cells that divide and expand to form the ventral embryonic surface. The spitz class genes are required for the proper formation of the larval ventral cuticle. Using a group of enhancer trap lines that stain subsets of epidermal cells, it is shown here that spitz class gene function is necessary for ventral epidermal development and gene expression. Analysis of single-minded mutant embryos implies that ventral epidermal cell fate is influenced by the CNS midline cells.

scholarly journals Cell and molecular biology of Notch

2007 ◽  
Vol 194 (3) ◽  
pp. 459-474 ◽  
Author(s):  
Ulla-Maj Fiúza ◽  
Alfonso Martinez Arias
Keyword(s):  
Cell Fate ◽  
Cell Communication ◽  
Notch Signalling ◽  
Multiple Roles ◽  
Communication Process ◽  
Regulatory Mechanisms ◽  
Cell Populations ◽  
Notch Signalling Pathway ◽  
A Cell ◽  
Stem Cell Populations

Notch signalling is a cell–cell communication process, which allows the establishment of patterns of gene expression and differentiation, regulates binary cell fate choice and the maintenance of stem cell populations. So far, the data published has elucidated the main players in the Notch signalling pathway. However, its regulatory mechanisms are exhibiting an increasing complexity which could account for the multitude of roles it has during development and in adult organisms. In this review, we will describe the multiple roles of Notch and how various factors can regulate Notch signalling.

scholarly journals EXPRESIÓN DE LOS GENES Serrate1 Y Notch1 DURANTE EL DESARROLLO DEL TERCIO MEDIO FACIAL DEL EMBRIÓN DE POLLO

2015 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel Mauricio Meza Lasso ◽  
Cindy Johana Peña Barrera ◽  
Francy Yomara Bayona Rodriguez ◽  
Belfran Alcides Carbonell Medina ◽  
Clementina Infante
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Expression Patterns ◽  
Notch Pathway ◽  
Cell Communication ◽  
Gallus Gallus ◽  
Notch Signaling Pathway ◽  
Cellular Processes

<p class="p1"><strong>RESUMEN</strong></p><p class="p2">La vía de señalización Notch se caracteriza por mediar la comunicación célula-célula, regulando diferentes procesos celulares como proliferación, apoptosis y definición del destino celular. Esta vía ha sido implicada en el desarrollo de estructuras craneofaciales como paladar, diente y bóveda craneal. El objetivo de esta investigación fue identificar los patrones de expresión de los genes componentes de la vía Notch, Serrate1 y Notch1, durante el desarrollo del tercio medio facial. Se utilizaron embriones de pollo (Gallus gallus) seleccionados de acuerdo a los criterios de Hamilton y Hamburger y sobre los cuales se realizó hibridación in situ con ribosondas marcadas con Digoxigenina (DIG), para luego ser detectadas con anticuerpos Anti-Dig. Los resultados mostraron expresión de los genes evaluados, en las prominencias maxilares (pmx) y frontonasal (pfn) durante el desarrollo del tercio medio facial. Estos resultados sugieren una probable participación de la vía Notch a través de estos genes, en los diferentes procesos celulares que determinan la morfogénesis y el desarrollo del tercio medio facial.</p><p class="p2"><strong>ABSTRACT</strong></p><p class="p2">The Notch signaling pathway is characterized by mediate cell-cell communication, regulating different cellular processes as proliferation, apoptosis and cell fate definition. This pathway has been implicated in craniofacial structures development as palate, teeth and cranial vault. The objective of this research was to identify the genes expression patterns of some Notch signaling pathway components, Serrate1 and Notch1, during the midface development. It was used chicken embryos (Gallus gallus) selected according to Hamilton and Hamburger criteria. We performed in situ hybridization with Digoxigenin (DIG)-labeled riboprobes and detected with the antibody Anti-Dig. The results showed the expression of the evaluated genes in the maxillary (pmx) and frontonasal (pfn) prominences during the midface development. These results suggest a probable involvement of the Notch pathway through these genes in different cellular processes that determine midface morphogenesis and development.</p><p class="p2"> </p>

The big brain gene of Drosophila functions to control the number of neuronal precursors in the peripheral nervous system

Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Y. Rao ◽  
R. Bodmer ◽  
L.Y. Jan ◽  
Y.N. Jan
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Cell Fate ◽  
Neural Development ◽  
Mutant Phenotype ◽  
Neurogenic Genes ◽  
Neuronal Precursors ◽  
Sensory Nervous System ◽  
The One ◽  
Multiple Stages

big brain (bib) is one of the six known zygotic neurogenic genes involved in the decision of an ectodermal cell to take on the neurogenic or the epidermogenic cell fate. Previous studies suggest that bib functions in a pathway separate from the one involving Notch and other known neurogenic genes. For a better understanding of the bib function, it is essential first to characterize the mutant phenotype in detail. Our mutant analyses show that loss of bib function approximately doubles the number of neuronal precursors and their progeny cells in the embryonic peripheral nervous system. Mosaic studies reveal a hypertrophy of sensory bristles in bib mutant patches in adult flies. Our observations are compatible with a function of bib in specifying neuronal precursors of both the embryonic and adult sensory nervous system. This is in contrast to the function of Notch, which continues to be required at multiple stages of neural development subsequent to this initial determination event.

scholarly journals Interplay Between Notch and YAP/TAZ Pathways in the Regulation of Cell Fate During Embryo Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Carolyn Engel-Pizcueta ◽  
Cristina Pujades
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
Notch Pathway ◽  
Cell Communication ◽  
Tissue Growth ◽  
General Mechanism ◽  
Dependent Manner ◽  
Cell Fate Decisions ◽  
Physical Cues ◽  
Progenitor Maintenance

Cells in growing tissues receive both biochemical and physical cues from their microenvironment. Growing evidence has shown that mechanical signals are fundamental regulators of cell behavior. However, how physical properties of the microenvironment are transduced into critical cell behaviors, such as proliferation, progenitor maintenance, or differentiation during development, is still poorly understood. The transcriptional co-activators YAP/TAZ shuttle between the cytoplasm and the nucleus in response to multiple inputs and have emerged as important regulators of tissue growth and regeneration. YAP/TAZ sense and transduce physical cues, such as those from the extracellular matrix or the actomyosin cytoskeleton, to regulate gene expression, thus allowing them to function as gatekeepers of progenitor behavior in several developmental contexts. The Notch pathway is a key signaling pathway that controls binary cell fate decisions through cell–cell communication in a context-dependent manner. Recent reports now suggest that the crosstalk between these two pathways is critical for maintaining the balance between progenitor maintenance and cell differentiation in different tissues. How this crosstalk integrates with morphogenesis and changes in tissue architecture during development is still an open question. Here, we discuss how progenitor cell proliferation, specification, and differentiation are coordinated with morphogenesis to construct a functional organ. We will pay special attention to the interplay between YAP/TAZ and Notch signaling pathways in determining cell fate decisions and discuss whether this represents a general mechanism of regulating cell fate during development. We will focus on research carried out in vertebrate embryos that demonstrate the important roles of mechanical cues in stem cell biology and discuss future challenges.

Barbu: an E(spl) m4/m(alpha)-related gene that antagonizes Notch signaling and is required for the establishment of ommatidial polarity

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 1115-1130 ◽  
Author(s):  
S. Zaffran ◽  
M. Frasch
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Sequence Similarity ◽  
Ectopic Expression ◽  
Notch Pathway ◽  
Imaginal Discs ◽  
Notch Receptor ◽  
Cell Type ◽  
Cell Fate Decisions ◽  
Signaling Activity

The Notch signaling pathway is required, in concert with cell-type-specific transcriptional regulators and other signaling processes, for multiple cell fate decisions during mesodermal and ectodermal tissue development. In many instances, Notch signaling occurs initially in a bidirectional manner and then becomes unidirectional upon amplification of small inherent differences in signaling activity between neighboring cells. In addition to ligands and extracellular modulators of the Notch receptor, several intracellular proteins have been identified that can positively or negatively influence the activity of the Notch pathway during these dynamic processes. Here, we describe a new gene, Barbu, whose product can antagonize Notch signaling activity during Drosophila development. Barbu encodes a small and largely cytoplasmic protein with sequence similarity to the proteins encoded by the transcription units m4 and m(alpha) of the E(spl) complex. Ectopic expression studies with Barbu provide evidence that Barbu can antagonize Notch during lateral inhibition processes in the embryonic mesoderm, sensory organ specification in imaginal discs and cell type specification in developing ommatidia. Barbu loss-of-function mutations cause lethality and disrupt the establishment of planar polarity and photoreceptor specification in eye imaginal discs, which may also be a consequence of altered Notch signaling activities. Furthermore, in the embryonic neuroectoderm, Barbu expression is inducible by activated Notch. Taken together, we propose that Barbu functions in a negative feed-back loop, which may be important for the accurate adjustment of Notch signaling activity and the extinction of Notch activity between successive rounds of signaling events.

scholarly journals Cadherins in early neural development

2021 ◽  
Author(s):  
Karolina Punovuori ◽  
Mattias Malaguti ◽  
Sally Lowell
Keyword(s):  
Adhesion Molecules ◽  
Cell Fate ◽  
Neural Development ◽  
Ex Vivo ◽  
Directed Differentiation ◽  
Culture Dish ◽  
Cell Identity ◽  
Cell Fate Decisions ◽  
Neural Tissues ◽  
And Function

AbstractDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

scholarly journals Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 521
Author(s):  
Catia Giovannini ◽  
Francesca Fornari ◽  
Fabio Piscaglia ◽  
Laura Gramantieri
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Hepatitis Virus ◽  
Notch Pathway ◽  
Notch Receptor ◽  
Gamma Secretase ◽  
Stem Cell Maintenance ◽  
Pathway Activation ◽  
Promising Therapeutic Approach ◽  
Conserved Genes

The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection. In this review, we briefly summarize the mechanisms involved in Notch pathway activation in HCC supporting the development of alternatives to the γ-secretase pan-inhibitor for HCC therapy.

Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 1154-1162 ◽  
Author(s):  
Wei Zheng ◽  
Tuomas Tammela ◽  
Masahiro Yamamoto ◽  
Andrey Anisimov ◽  
Tanja Holopainen ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Target Genes ◽  
Notch Pathway ◽  
Lymphatic Vessels ◽  
Soluble Form ◽  
Fibrin Gel ◽  
3 Dimensional ◽  
Endothelial Growth Factor

Abstract Notch signaling plays a central role in cell-fate determination, and its role in lateral inhibition in angiogenic sprouting is well established. However, the role of Notch signaling in lymphangiogenesis, the growth of lymphatic vessels, is poorly understood. Here we demonstrate Notch pathway activity in lymphatic endothelial cells (LECs), as well as induction of delta-like ligand 4 (Dll4) and Notch target genes on stimulation with VEGF or VEGF-C. Suppression of Notch signaling by a soluble form of Dll4 (Dll4-Fc) synergized with VEGF in inducing LEC sprouting in 3-dimensional (3D) fibrin gel assays. Expression of Dll4-Fc in adult mouse ears promoted lymphangiogenesis, which was augmented by coexpressing VEGF. Lymphangiogenesis triggered by Notch inhibition was suppressed by a monoclonal VEGFR-2 Ab as well as soluble VEGF and VEGF-C/VEGF-D ligand traps. LECs transduced with Dll4 preferentially adopted the tip cell position over nontransduced cells in 3D sprouting assays, suggesting an analogous role for Dll4/Notch in lymphatic and blood vessel sprouting. These results indicate that the Notch pathway controls lymphatic endothelial quiescence, and explain why LECs are poorly responsive to VEGF compared with VEGF-C. Understanding the role of the Notch pathway in lymphangiogenesis provides further insight for the therapeutic manipulation of the lymphatic vessels.

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