The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3363-3370 ◽  
Author(s):  
M. Golembo ◽  
E. Raz ◽  
B.Z. Shilo
Keyword(s):  
Feedback Loop ◽  
Egf Receptor ◽  
Ectopic Expression ◽  
Cell Fates ◽  
Inhibitory Feedback ◽  
Midline Cells ◽  
Stable Source

The Drosophila EGF receptor (DER) is activated by secreted Spitz to induce different cell fates in the ventral ectoderm. Processing of the precursor transmembrane Spitz to generate the secreted form was shown to be the limiting event, but the cells in which processing takes place and the mechanism that may generate a gradient of secreted Spitz in the ectoderm were not known. The ectodermal defects in single minded (sim) mutant embryos, in which the midline fails to develop, suggested that the midline cells contribute to patterning of the ventral ectoderm. This work shows that the midline provides the site for Spitz expression and processing. The Rhomboid and Star proteins are also expressed and required in the midline. The ectodermal defects of spitz, rho or Star mutant embryos could be rescued by inducing the expression of the respective normal genes only in the midline cells. Rho and Star thus function non-autonomously, and may be required for the production or processing of the Spitz precursor. Secreted Spitz is the only sim-dependent contribution of the midline to patterning the ectoderm, since the ventral defects observed in sim mutant embryos can be overcome by expression of secreted Spitz in the ectoderm. While ectopic expression of secreted Spitz in the ectoderm or mesoderm gave rise to ventralization of the embryo, increased expression of secreted Spitz in the midline did not lead to alterations in ectoderm patterning. A mechanism for adjustment to variable levels of secreted Spitz emanating from the midline may be provided by Argos, which forms an inhibitory feedback loop for DER activation. The production of secreted Spitz in the midline, may provide a stable source for graded DER activation in the ventral ectoderm.

Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 223-230 ◽  
Author(s):  
M. Golembo ◽  
R. Schweitzer ◽  
M. Freeman ◽  
B.Z. Shilo
Keyword(s):  
Cell Culture ◽  
Signaling Pathways ◽  
Feedback Loop ◽  
Egf Receptor ◽  
Cell Fates ◽  
Inhibitory Feedback

Argos is a secreted molecule with an atypical EGF motif. It was recently shown to function as an inhibitor of the signaling triggered by the Drosophila EGF receptor (DER). In this work, we determine the contribution of Argos to the establishment of cell fates in the embryonic ventral ectoderm. Graded activation of DER is essential for patterning the ventral ectoderm. argos mutant embryos show expansion of ventral cell fates suggesting hyperactivation of the DER pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells. We show that argos expression in the ventral ectoderm is induced by the DER pathway: argos is not expressed in DER mutant embryos, while it is ectopically expressed in the entire ventral ectoderm following ubiquitous activation of the DER pathway. argos expression appears to be triggered directly by the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling. This type of inhibitory feedback loop may represent a general paradigm for signaling pathways inducing diverse cell fates within a population of non-committed cells.

Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 191-200 ◽  
Author(s):  
A. Sapir ◽  
R. Schweitzer ◽  
B.Z. Shilo
Keyword(s):  
Target Genes ◽  
Egf Receptor ◽  
Ectopic Expression ◽  
Follicle Cell ◽  
Follicle Cells ◽  
Cell Fates ◽  
Dorsoventral Axis ◽  
Spatial Coordinates ◽  
Sequential Activation

Previous work has demonstrated a role for the Drosophila EGF receptor (Torpedo/DER) and its ligand, Gurken, in the determination of anterioposterior and dorsoventral axes of the follicle cells and oocyte. The roles of DER in establishing the polarity of the follicle cells were examined further, by following the expression of DER-target genes. One class of genes (e.g. kekon) is induced by the DER pathway at all stages. Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows. This may provide the spatial coordinates for the ventral-most follicle cell fates. A second group of target genes (e.g. rhomboid (rho)) is induced only at later stages of oogenesis, and may require additional inputs by signals emanating from the anterior, stretch follicle cells. The function of Rho was analyzed by ectopic expression in the stretch follicle cells, and shown to induce a non-autonomous dorsalizing activity that is independent of Gurken. Rho thus appears to be involved in processing a DER ligand in the follicle cells, to pattern the egg chamber and allow persistent activation of the DER pathway during formation of the dorsal appendages.

scholarly journals Landscape of epithelial-mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks

2021 ◽  
Author(s):  
Kishore Hari ◽  
Varun Ullanat ◽  
Archana Balasubramanian ◽  
Aditi Gopalan ◽  
Mohit Kumar Jolly
Keyword(s):  
Decision Making ◽  
Regulatory Networks ◽  
Feedback Loop ◽  
Emergent Property ◽  
Toggle Switch ◽  
Cell Fates ◽  
Cellular Decision Making ◽  
Inhibitory Feedback ◽  
Decision Making Processes ◽  
Simple Network

Elucidating the principles of cellular decision-making is of fundamental importance. These decisions are often orchestrated by underlying regulatory networks. While we understand the dynamics of simple network motifs, how do large networks lead to a limited number of phenotypes, despite their complexity, remains largely elusive. Here, we investigate five different networks governing epithelial-mesenchymal plasticity and identified a latent design principles in their topology that limits their phenotypic repertoire - the presence of two 'teams' of nodes engaging in a mutually inhibitory feedback loop, forming a toggle switch. These teams are specific to these networks and directly shape the phenotypic landscape and consequently the frequency and stability of terminal phenotypes vs. the intermediary ones. Our analysis reveals that network topology alone can contain information about phenotypic distributions it can lead to, thus obviating the need to simulate them. We unravel topological signatures that can drive canalization of cell-fates during diverse decision-making processes.

Inhibitory Feedback Loop Induces Anticipated Synchronization in Neuronal Networks

2014 ◽  
Vol 1 ◽  
pp. 636-639
Author(s):  
Fernanda S. Matias ◽  
Pedro V. Carelli ◽  
Claudio R. Mirasso ◽  
Mauro Copelli
Keyword(s):  
Feedback Loop ◽  
Neuronal Networks ◽  
Inhibitory Feedback

split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1517-1529 ◽  
Author(s):  
B. Kuang ◽  
S.C. Wu ◽  
Y. Shin ◽  
L. Luo ◽  
P. Kolodziej
Keyword(s):  
Cell Fate ◽  
Egf Receptor ◽  
Neuronal Cell ◽  
Drosophila Embryo ◽  
Neuronal Precursors ◽  
Split Ends ◽  
Recognition Motifs ◽  
Midline Cells ◽  
Wrong Number ◽  
Nuclear Levels

split ends (spen) encodes nuclear 600 kDa proteins that contain RNA recognition motifs and a conserved C-terminal sequence. These features define a new protein family, Spen, which includes the vertebrate MINT transcriptional regulator. Zygotic spen mutants affect the growth and guidance of a subset of axons in the Drosophila embryo. Removing maternal and zygotic protein elicits cell-fate and more general axon-guidance defects that are not seen in zygotic mutants. The wrong number of chordotonal neurons and midline cells are generated, and we identify defects in precursor formation and EGF receptor-dependent inductive processes required for cell-fate specification. The number of neuronal precursors is variable in embryos that lack Spen. The levels of Suppressor of Hairless, a key transcriptional effector of Notch required for precursor formation, are reduced, as are the nuclear levels of Yan, a transcriptional repressor that regulates cell fate and proliferation downstream of the EGF receptor. We propose that Spen proteins regulate the expression of key effectors of signaling pathways required to specify neuronal cell fate and morphology.

EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3355-3362 ◽  
Author(s):  
L. Gabay ◽  
H. Scholz ◽  
M. Golembo ◽  
A. Klaes ◽  
B.Z. Shilo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Egf Receptor ◽  
Protein A ◽  
Drosophila Embryo ◽  
Cell Fates ◽  
Secondary Target ◽  
Graded Activity ◽  
Definition Of

The induction of different cell fates along the dorsoventral axis of the Drosophila embryo requires a graded activity of the EGF receptor tyrosine kinase (DER). Here we have identified primary and secondary target genes of DER, which mediate the determination of discrete ventral cell fates. High levels of DER activation in the ventralmost cells trigger expression of the transcription factors encoded by ventral nervous system defective (vnd) and pointed P1 (pntPl). Concomitant with the induction of pntP1, high levels of DER activity lead to inactivation of the Yan protein, a transcriptional repressor of Pointed-target genes. These two antagonizing transcription factors subsequently control the expression of secondary target genes such as otd, argos and tartan. The simultaneous effects of the DER pathway on pntP1 induction and Yan inactivation may contribute to the definition of the border of the ventralmost cell fates.

Misexpression of chick Vg1 in the marginal zone induces primitive streak formation

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5127-5138 ◽  
Author(s):  
S.B. Shah ◽  
I. Skromne ◽  
C.R. Hume ◽  
D.S. Kessler ◽  
K.J. Lee ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Ectopic Expression ◽  
Primitive Streak ◽  
Axis Formation ◽  
Mesoderm Induction ◽  
Cell Fates ◽  
Signalling Molecules ◽  
Posterior Area ◽  
Area Pellucida

In the chick embryo, the primitive streak is the first axial structure to develop. The initiation of primitive streak formation in the posterior area pellucida is influenced by the adjacent posterior marginal zone (PMZ). We show here that chick Vg1 (cVg1), a member of the TGFbeta family of signalling molecules whose homolog in Xenopus is implicated in mesoderm induction, is expressed in the PMZ of prestreak embryos. Ectopic expression of cVg1 protein in the marginal zone chick blastoderms directs the formation of a secondary primitive streak, which subsequently develops into an ectopic embryo. We have used cell marking techniques to show that cells that contribute to the ectopic primitive streak change fate, acquiring two distinct properties of primitive streak cells, defined by gene expression and cell movements. Furthermore, naive epiblast explants exposed to cVg1 protein in vitro acquire axial mesodermal properties. Together, these results show that cVg1 can mediate ectopic axis formation in the chick by inducing new cell fates and they permit the analysis of distinct events that occur during primitive streak formation.

An epidermal growth factor receptor/ret chimera generates mitogenic and transforming signals: evidence for a ret-specific signaling pathway

1994 ◽  
Vol 14 (1) ◽  
pp. 663-675
Author(s):  
M Santoro ◽  
W T Wong ◽  
P Aroca ◽  
E Santos ◽  
B Matoskova ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Mammalian Cells ◽  
Egf Receptor ◽  
Biological Effects ◽  
Ectopic Expression ◽  
Growth Factor Receptor ◽  
Dependent Signal ◽  
Epidermal Growth

A chimeric expression vector which encoded for a molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) and the intracellular domain of the ret kinase (EGFR/ret chimera) was generated. Upon ectopic expression in mammalian cells, the EGFR/ret chimera was correctly synthesized and transported to the cell surface, where it was shown capable of binding EGF and transducing an EGF-dependent signal intracellularly. Thus, the EGFR/ret chimera allows us to study the biological effects and biochemical activities of the ret kinase under controlled conditions of activation. Comparative analysis of the growth-promoting activity of the EGFR/ret chimera expressed in fibroblastic or hematopoietic cells revealed a biological phenotype clearly distinguishable from that of the EGFR, indicating that the two kinases couple with mitogenic pathways which are different to some extent. Analysis of biochemical pathways implicated in the transduction of mitogenic signals also evidenced significant differences between the ret kinase and other receptor tyrosine kinases. Thus, the sum of our results indicates the existence of a ret-specific pathway of mitogenic signaling.

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