Lateral inhibition and the development of the sensory bristles of the adult peripheral nervous system of Drosophila

Development ◽  
1990 ◽  
Vol 109 (3) ◽  
pp. 509-519 ◽  
Author(s):  
P. Simpson
Keyword(s):  
Small Groups ◽  
Neural Cells ◽  
Cellular Interactions ◽  
Equivalence Group ◽  
Neural Fate ◽  
Neurogenic Genes ◽  
Sensory Bristles ◽  
Proneural Cluster ◽  
Molecular Nature ◽  
Bristle Pattern

Cells in the neurectoderm of Drosophila face a choice between neural and epidermal fates. On the notum of the adult fly, neural cells differentiate sensory bristles in a precise pattern. Evidence has accumulated that the bristle pattern arises from the spatial distribution of small groups of cells, proneural clusters, from each of which a single bristle will result. One class of genes, which includes the genes of the achaete-scute complex, is responsible for the correct positioning of the proneural clusters. The cells of a proneural cluster constitute an equivalence group, each of them having the potential to become a neural cell. Only one cell, however, will adopt the primary, dominant, neural fate. This cell is selected by means of cellular interactions between the members of the group, since if the dominant cell is removed, one of the remaining, epidermal, cells will switch fates and become neural. The dominant cell therefore prevents the other cells of the group from becoming neural by a phenomenon known as lateral inhibiton. They, then, adopt the secondary, epidermal, fate. A second class of genes, including the gene shaggy and the neurogenic genes mediate this process. There is some evidence that a proneural cluster is composed of a small number of cells, suggesting a contact-based mechanism of communication. The molecular nature of the protein products of the neurogenic genes is consistent with this idea.

Proneural clusters: equivalence groups in the epithelium of Drosophila

Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 927-932 ◽  
Author(s):  
P. Simpson ◽  
C. Carteret
Keyword(s):  
Nervous System ◽  
Cell Lineage ◽  
Cellular Interactions ◽  
Equivalence Group ◽  
Neural Fate ◽  
Axonal Projections ◽  
The Central Nervous System ◽  
Neuronal Specificity ◽  
Proneural Cluster ◽  
Do So

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.

scholarly journals Antagonism of EGFR and notch signalling in the reiterative recruitment of Drosophila adult chordotonal sense organ precursors

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3149-3157 ◽  
Author(s):  
P. zur Lage ◽  
A.P. Jarman
Keyword(s):  
Lateral Inhibition ◽  
Single Cells ◽  
Growth Factor Receptor ◽  
Sense Organ ◽  
Notch Signalling ◽  
Equivalence Group ◽  
Neural Fate ◽  
Epidermal Growth ◽  
Sensory Bristles ◽  
Proneural Cluster

The selection of Drosophila melanogaster sense organ precursors (SOPs) for sensory bristles is a progressive process: each neural equivalence group is transiently defined by the expression of proneural genes (proneural cluster), and neural fate is refined to single cells by Notch-Delta lateral inhibitory signalling between the cells. Unlike sensory bristles, SOPs of chordotonal (stretch receptor) sense organs are tightly clustered. Here we show that for one large adult chordotonal SOP array, clustering results from the progressive accumulation of a large number of SOPs from a persistent proneural cluster. This is achieved by a novel interplay of inductive epidermal growth factor-receptor (EGFR) and competitive Notch signals. EGFR acts in opposition to Notch signalling in two ways: it promotes continuous SOP recruitment despite lateral inhibition, and it attenuates the effect of lateral inhibition on the proneural cluster equivalence group, thus maintaining the persistent proneural cluster. SOP recruitment is reiterative because the inductive signal comes from previously recruited SOPs.

scholarly journals Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 299 ◽  
Author(s):  
Liqing Song ◽  
Yuanwei Yan ◽  
Mark Marzano ◽  
Yan Li
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Human Brain ◽  
Neurodegenerative Disease ◽  
Disease Progression ◽  
Cell Types ◽  
Neural Cells ◽  
Cellular Interactions ◽  
Induced Pluripotent

Human cerebral organoids derived from induced pluripotent stem cells (iPSCs) provide novel tools for recapitulating the cytoarchitecture of the human brain and for studying biological mechanisms of neurological disorders. However, the heterotypic interactions of neurovascular units, composed of neurons, pericytes (i.e., the tissue resident mesenchymal stromal cells), astrocytes, and brain microvascular endothelial cells, in brain-like tissues are less investigated. In addition, most cortical organoids lack a microglia component, the resident immune cells in the brain. Impairment of the blood-brain barrier caused by improper crosstalk between neural cells and vascular cells is associated with many neurodegenerative disorders. Mesenchymal stem cells (MSCs), with a phenotype overlapping with pericytes, have promotion effects on neurogenesis and angiogenesis, which are mainly attributed to secreted growth factors and extracellular matrices. As the innate macrophages of the central nervous system, microglia regulate neuronal activities and promote neuronal differentiation by secreting neurotrophic factors and pro-/anti-inflammatory molecules. Neuronal-microglia interactions mediated by chemokines signaling can be modulated in vitro for recapitulating microglial activities during neurodegenerative disease progression. In this review, we discussed the cellular interactions and the physiological roles of neural cells with other cell types including endothelial cells and microglia based on iPSC models. The therapeutic roles of MSCs in treating neural degeneration and pathological roles of microglia in neurodegenerative disease progression were also discussed.

scholarly journals Embryonic stem cells assume a primitive neural stem cell fate in the absence of extrinsic influences

2006 ◽  
Vol 172 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Simon R. Smukler ◽  
Susan B. Runciman ◽  
Shunbin Xu ◽  
Derek van der Kooy
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Es Cells ◽  
Embryonic Stem ◽  
Neural Cells ◽  
Neural Fate ◽  
Default State ◽  
Genetic Interference ◽  
Will Self

The mechanisms governing the emergence of the earliest mammalian neural cells during development remain incompletely characterized. A default mechanism has been suggested to underlie neural fate acquisition; however, an instructive process has also been proposed. We used mouse embryonic stem (ES) cells to explore the fundamental issue of how an uncommitted, pluripotent mammalian cell will self-organize in the absence of extrinsic signals and what cellular fate will result. To assess this default state, ES cells were placed in conditions that minimize external influences. Individual ES cells were found to rapidly transition directly into neural cells, a process shown to be independent of suggested instructive factors (e.g., fibroblast growth factors). Further, we provide evidence that the default neural identity is that of a primitive neural stem cell (NSC). The exiguous conditions used to reveal the default state were found to present primitive NSCs with a survival challenge (limiting their persistence and proliferation), which could be mitigated by survival factors or genetic interference with apoptosis.

scholarly journals The Evolution of the Neural Basic Helix-Loop-Helix Proteins

2001 ◽  
Vol 1 ◽  
pp. 396-426 ◽  
Author(s):  
Michel Vervoort ◽  
Valerie Ledent
Keyword(s):  
Expression Patterns ◽  
Neural Cells ◽  
Specific Expression ◽  
Neural Fate ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Neuronal Precursors ◽  
Vertebrate Orthologs ◽  
Mature Neurons

Basic Helix-Loop-Helix (bHLH) transcription factors control various aspects of the formation of the nervous system in the metazoans. In Drosophila some bHLH (such as the achaete-scuteatonal, and amos genes) act as proneural genes, directing ectodermal cells toward a neural fate. Their vertebrate orthologs, however, probably do not assume such a neural determination function, but rather control the decision made by neural precursors to generate neurons and not glial cells, as well as the progression of neuronal precursors toward differentiation into mature neurons. The proneural function of Drosophila bHLH genes may be an innovation that occurs in the evolutive lineage that leads to arthropods. In addition, although neural bHLH appear to be involved in the specification of neuronal identities, they probably do not confer by themselves neuronal type-specific properties to the cells. Rather, neural bHLH allow neural cells to correctly interpret specification and positional cues provided by other factors. Although bHLH genes are often expressed in complementary subsets of neural cells and/or expressed sequentially in those cells, the coding regions of the various neural bHLH appear largely interchangeable. We propose that the specific expression patterns have been acquired, following gene duplications, by subfunctional-ization, i.e., the partitioning of ancestral expression patterns among the duplicates and, by extension, we propose that subfunctionalization is a key process to understand the evolution of neural bHLH genes.

scholarly journals From Brain Organoids to Networking Assembloids: Implications for Neuroendocrinology and Stress Medicine

2021 ◽  
Vol 12 ◽  
Author(s):  
Evanthia A. Makrygianni ◽  
George P. Chrousos
Keyword(s):  
Three Dimensional ◽  
Neural Circuitry ◽  
Brain Regions ◽  
Stress System ◽  
Neural Cells ◽  
Main Task ◽  
Cellular Interactions ◽  
Cell Lineages ◽  
Brain Organoid ◽  
Development Regulation

Brain organoids are three-dimensional cultures that contain multiple types of cells and cytoarchitectures, and resemble fetal human brain structurally and functionally. These organoids are being used increasingly to model brain development and disorders, however, they only partially recapitulate such processes, because of several limitations, including inability to mimic the distinct cortical layers, lack of functional neuronal circuitry as well as non-neural cells and gyrification, and increased cellular stress. Efforts to create improved brain organoid culture systems have led to region-specific organoids, vascularized organoids, glia-containing organoids, assembloids, sliced organoids and polarized organoids. Assembloids are fused region-specific organoids, which attempt to recapitulate inter-regional and inter-cellular interactions as well as neural circuitry development by combining multiple brain regions and/or cell lineages. As a result, assembloids can be used to model subtle functional aberrations that reflect complex neurodevelopmental, neuropsychiatric and neurodegenerative disorders. Mammalian organisms possess a highly complex neuroendocrine system, the stress system, whose main task is the preservation of systemic homeostasis, when the latter is threatened by adverse forces, the stressors. The main central parts of the stress system are the paraventricular nucleus of the hypothalamus and the locus caeruleus/norepinephrine-autonomic nervous system nuclei in the brainstem; these centers innervate each other and interact reciprocally as well as with various other CNS structures. Chronic dysregulation of the stress system has been implicated in major pathologies, the so-called chronic non-communicable diseases, including neuropsychiatric, neurodegenerative, cardiometabolic and autoimmune disorders, which lead to significant population morbidity and mortality. We speculate that brain organoids and/or assembloids could be used to model the development, regulation and dysregulation of the stress system and to better understand stress-related disorders. Novel brain organoid technologies, combined with high-throughput single-cell omics and gene editing, could, thus, have major implications for precision medicine.

Cell commitment and cell interactions in the ectoderm of Drosophila melanogaster

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 39-46 ◽  
Author(s):  
Isabella Stüttem ◽  
José A. Campos-Ortega
Keyword(s):  
Drosophila Melanogaster ◽  
Progenitor Cells ◽  
Epidermal Cells ◽  
Cellular Interactions ◽  
Heterotopic Transplantation ◽  
Anterior Pole ◽  
Neural Fate ◽  
Cell Commitment ◽  
Anterior Midgut

The separation of neural from epidermal progenitor cells in the ventral neuroectoderm of Drosophila is thought to be mediated by cellular interactions. In order to verify the occurrence of regulatory signals and to test the neurogenic capabilities of cells from various regions of the ectoderm, we have carried out homotopic and heterotopic transplantations of single ectodermal cells. We found that cells from any of the tested regions, with the exception of the proctodeal anlage, are capable of developing as neuroblasts following their transplantation into the ventral neuroectoderm. These neurogenic capabilities are gradually distributed. Cells from the procephalic and ventral neurogenic regions exhibit maximal capabilities, as shown by their behavior in heterotopic transplantations. However, the two neurogenic regions differ from each other in that no epidermalising signals can be demonstrated to occur within the procephalic neuroectoderm, whereas such signals are strong within the ventral neuroectoderm; in addition, neuralising signals from neighbouring cells seem to be necessary for neuroectodermal cells to develop as neuroblasts. Other ectodermal regions whose cells exhibit weaker neurogenic capabilities are, in decreasing order of capability, the dorsal epidermal anlage, the anterolateral region of the procephalic lobe, comprising the anlage of the pharynx, and the anterior pole of the embryo, corresponding to the anlagen of the stomodeum and ectodermal anterior midgut. We assume that, during development in situ, the neurogenic capabilities of all these cells are suppressed by inhibitory signals, which are released upon heterotopic transplantation into the neuroectoderm. A community effect which prevents groups of dorsal epidermal cells from taking on a neural fate upon their transplantation into the ventral neuroectoderm, is shown. Finally, we hypothesize that the lack of neurogenic capability in the cells from the proctodeal anlage is due to the absence of products of the proneural genes.

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.

scholarly journals Cell-to-Cell Interactions Mediating Functional Recovery after Stroke

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3050
Author(s):  
Claudia Alia ◽  
Daniele Cangi ◽  
Verediana Massa ◽  
Marco Salluzzo ◽  
Livia Vignozzi ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Cell Interactions ◽  
Neural Cells ◽  
Cellular Interactions ◽  
Post Stroke ◽  
Wide Range ◽  
Structural Plastic ◽  
Novel Therapeutic Strategies ◽  
Intercellular Connections

Ischemic damage in brain tissue triggers a cascade of molecular and structural plastic changes, thus influencing a wide range of cell-to-cell interactions. Understanding and manipulating this scenario of intercellular connections is the Holy Grail for post-stroke neurorehabilitation. Here, we discuss the main findings in the literature related to post-stroke alterations in cell-to-cell interactions, which may be either detrimental or supportive for functional recovery. We consider both neural and non-neural cells, starting from astrocytes and reactive astrogliosis and moving to the roles of the oligodendrocytes in the support of vulnerable neurons and sprouting inhibition. We discuss the controversial role of microglia in neural inflammation after injury and we conclude with the description of post-stroke alterations in pyramidal and GABAergic cells interactions. For all of these sections, we review not only the spontaneous evolution in cellular interactions after ischemic injury, but also the experimental strategies which have targeted these interactions and that are inspiring novel therapeutic strategies for clinical application.

Functional analysis of an ascidian homologue of vertebrate Bmp-2/Bmp-4 suggests its role in the inhibition of neural fate specification

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5149-5159 ◽  
Author(s):  
T. Miya ◽  
K. Morita ◽  
A. Suzuki ◽  
N. Ueno ◽  
N. Satoh
Keyword(s):  
Sequence Similarity ◽  
Neural Tissue ◽  
Muscle Cells ◽  
Cell Interaction ◽  
Cellular Interaction ◽  
Cellular Interactions ◽  
Halocynthia Roretzi ◽  
Functional Conservation ◽  
Neural Fate ◽  
Mode Of Development

The ascidian tadpole larva is thought to be close to a prototype of the ancestral chordate. The vertebrate body plan is established by a series of inductive cellular interactions, whereas ascidians show a highly determinate mode of development. Recent studies however, suggest some roles of cell-cell interaction during ascidian embryogenesis. To elucidate the signaling molecules responsible for the cellular interaction, we isolated HrBMPb, an ascidian homologue of the vertebrate bone morphogenetic protein (BMP) gene, from Halocynthia roretzi. The amino acid sequence of HrBMPb closely resembled those of vertebrate BMP-2 and BMP-4 and of Drosophila Decapentaplegic (DPP). In addition to the sequence similarity, HrBMPb overexpression induced the ventralization of Xenopus embryos, suggesting functional conservation. The zygotic expression of HrBMPb was first detected around gastrulation. HrBMPb expression was maintained in some cells at the lateral edges of the neural plate through gastrulation to neurulation, although that in the presumptive muscle cells was downregulated. HrBMPb was not expressed in the presumptive epidermis during gastrulation. When HrBMPb mRNA was injected into fertilized Halocynthia eggs, cells that normally give rise to the neural tissue differentiated into epidermis, causing a loss of anterior neural tissue in the larva. In addition, HrBMPb might function synergistically with HrBMPa, an ascidian homologue of BMPs-5 to 8. However, HrBMPb overexpression did not affect differentiation of the notochord and muscle cells. These results suggest that HrBMPb functions as a neural inhibitor and as an epidermal inducer but not as a ventralizing agent in ascidian development.

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