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

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.

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

Development ◽

10.1242/dev.109.3.509 ◽

1990 ◽

Vol 109 (3) ◽

pp. 509-519 ◽

Cited By ~ 33

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.

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Proneural clusters: equivalence groups in the epithelium of Drosophila

Development ◽

10.1242/dev.110.3.927 ◽

1990 ◽

Vol 110 (3) ◽

pp. 927-932 ◽

Cited By ~ 3

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.

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Multiple delta genes and lateral inhibition in zebrafish primary neurogenesis

Development ◽

10.1242/dev.125.3.359 ◽

1998 ◽

Vol 125 (3) ◽

pp. 359-370 ◽

Cited By ~ 20

Author(s):

C. Haddon ◽

L. Smithers ◽

S. Schneider-Maunoury ◽

T. Coche ◽

D. Henrique ◽

...

Keyword(s):

Lateral Inhibition ◽

Notch Signalling ◽

Neural Plate ◽

Primary Neurons ◽

Mauthner Cell ◽

Neural Fate ◽

Competitive Mechanism ◽

Neuroepithelial Cells ◽

Drosophila Cells ◽

Primary Neurogenesis

In Drosophila, cells are thought to be singled out for a neural fate through a competitive mechanism based on lateral inhibition mediated by Delta-Notch signalling. In tetrapod vertebrates, nascent neurons express the Delta1 gene and thereby deliver lateral inhibition to their neighbours, but it is not clear how these cells are singled out within the neurectoderm in the first place. We have found four Delta homologues in the zebrafish--twice as many as reported in any tetrapod vertebrate. Three of these--deltaA, deltaB and deltaD--are involved in primary neurogenesis, while two--deltaC and deltaD--appear to be involved in somite development. In the neural plate, deltaA and deltaD, unlike Delta1 in tetrapods, are expressed in large patches of contiguous cells, within which scattered individuals expressing deltaB become singled out as primary neurons. By gene misexpression experiments, we show: (1) that the singling-out of primary neurons, including the unique Mauthner cell on each side of the hindbrain, depends on Delta-Notch-mediated lateral inhibition, (2) that deltaA, deltaB and deltaD all have products that can deliver lateral inhibition and (3) that all three of these genes are themselves subject to negative regulation by lateral inhibition. These properties imply that competitive lateral inhibition, mediated by coordinated activities of deltaA, deltaB and deltaD, is sufficient to explain how primary neurons emerge from proneural clusters of neuroepithelial cells in the zebrafish.

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Cells use molecular working memory to navigate in changing chemoattractant fields

10.1101/2021.11.11.468222 ◽

2021 ◽

Author(s):

Akhilesh Nandan ◽

Abhishek Das ◽

Robert Lott ◽

Aneta Koseska

Keyword(s):

Working Memory ◽

Chemical Cues ◽

Single Cells ◽

Growth Factor Receptor ◽

Signal Source ◽

Egfr Signaling ◽

Stable States ◽

Migration Direction ◽

Epidermal Growth ◽

Local Gradient

In order to migrate over large distances, cells within tissues and organisms rely on sensing local gradient cues. These cues however are multifarious, irregular or conflicting, changing both in time and space. Here we find that single cells utilize a molecular mechanism akin to a working memory, to generate persistent directional migration when signals are disrupted by temporally memorizing their position, while still remaining adaptive to spatial and temporal changes of the signal source. Using dynamical systems theory, we derive that these information processing capabilities are inherent for protein networks whose dynamics is maintained away from steady state through organization at criticality. We demonstrate experimentally using the Epidermal growth factor receptor (EGFR) signaling network, that the memory is maintained in the prolonged activity of the receptor via a slow-escaping remnant, a dynamical ghost of the attractor of the polarized signaling state, that further results in memory in migration. As this state is metastable, it also enables continuous adaptation of the migration direction when the signals vary in space and time. We therefore show that cells implement real-time computations without stable-states to navigate in changing chemoattractant fields by memorizing position of disrupted signals while maintaining sensitivity to novel chemical cues.

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