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Research article
Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster
Vincent MIrouse
CNRS
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5823-342X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Developmental Biology.
Background : Scaffold proteins support a variety of key processes during animal development. Mutant mouse for the MAGUK protein Discs large 5 (Dlg5) presents a general growth impairment and moderate morphogenetic defects.
Results : Here, we generated null mutants for Drosophila Dlg5 and show that it owns similar functions in growth and epithelial architecture. Dlg5 is required for growth at a cell autonomous level in several tissues and at the organism level, affecting cell size and proliferation. Our results are consistent with Dlg5 modulating hippo pathway in the wing disc, including the impact on cell size, a defect that is reproduced by the loss of yorkie. However, other observations indicate that Dlg5 regulates growth by at least another way that may involve Myc protein but nor PI3K neither TOR pathways. Moreover, epithelia cells mutant for Dlg5 also show a reduction of apical domain determinants, though not sufficient to induce a complete loss of cell polarity. Dlg5 is also essential, in the same cells, for the presence at Adherens junctions of N-Cadherin, but not E-Cadherin. Genetic analyses indicate that junction and polarity defects are independent.
Conclusions : Together our data show that Dlg5 own several conserved functions that are independent of each other in regulating growth, cell polarity and cell adhesion. Moreover, they reveal a differential regulation of E-cadherin and N-cadherin apical localization.
Keywords
Drosophila, MAGUK, yorkie, hippo, myc, polarity, adhesion, growth
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Posted 12 May, 2020
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Editorial decision: Minor revision
On 24 Apr, 2020
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On 14 Apr, 2020
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On 13 Apr, 2020
Editor invited
On 13 Apr, 2020
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Editorial decision: Major revision
On 25 Mar, 2020
Reviewer #3 agreed
On 22 Mar, 2020
Review #3 received
Received 22 Mar, 2020
Review #2 received
Received 22 Mar, 2020
Reviewer #2 agreed
On 17 Mar, 2020
Review #1 received
Received 15 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Editor assigned
On 25 Feb, 2020
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On 24 Feb, 2020
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Editor invited
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This preprint is under consideration at BMC Developmental Biology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster
Vincent MIrouse
CNRS
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5823-342X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 3
Posted 12 May, 2020
No comments provided
Editorial decision: Minor revision
On 24 Apr, 2020
Editor assigned
On 14 Apr, 2020
Submission checks complete
On 13 Apr, 2020
Editor invited
On 13 Apr, 2020
No comments provided
Editorial decision: Major revision
On 25 Mar, 2020
Reviewer #3 agreed
On 22 Mar, 2020
Review #3 received
Received 22 Mar, 2020
Review #2 received
Received 22 Mar, 2020
Reviewer #2 agreed
On 17 Mar, 2020
Review #1 received
Received 15 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Editor assigned
On 25 Feb, 2020
First submitted
On 24 Feb, 2020
Submission checks complete
On 24 Feb, 2020
Editor invited
On 24 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Developmental Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Developmental Biology.
Background : Scaffold proteins support a variety of key processes during animal development. Mutant mouse for the MAGUK protein Discs large 5 (Dlg5) presents a general growth impairment and moderate morphogenetic defects.
Results : Here, we generated null mutants for Drosophila Dlg5 and show that it owns similar functions in growth and epithelial architecture. Dlg5 is required for growth at a cell autonomous level in several tissues and at the organism level, affecting cell size and proliferation. Our results are consistent with Dlg5 modulating hippo pathway in the wing disc, including the impact on cell size, a defect that is reproduced by the loss of yorkie. However, other observations indicate that Dlg5 regulates growth by at least another way that may involve Myc protein but nor PI3K neither TOR pathways. Moreover, epithelia cells mutant for Dlg5 also show a reduction of apical domain determinants, though not sufficient to induce a complete loss of cell polarity. Dlg5 is also essential, in the same cells, for the presence at Adherens junctions of N-Cadherin, but not E-Cadherin. Genetic analyses indicate that junction and polarity defects are independent.
Conclusions : Together our data show that Dlg5 own several conserved functions that are independent of each other in regulating growth, cell polarity and cell adhesion. Moreover, they reveal a differential regulation of E-cadherin and N-cadherin apical localization.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6