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The RNA helicase Ddx21 controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 function

Koltowska, Katarzyna (author)
Uppsala universitet,Vaskulärbiologi,Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia
Okuda, Kazuhide S. (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia; Peter MacCallum Canc Ctr, Melbourne, Vic, Australia; Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Gloger, Marleen (author)
Uppsala universitet,Vaskulärbiologi
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Rondon-Galeano, Maria (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.;Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
Mason, Elizabeth (author)
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
Xuan, Jiachen (author)
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
Dudczig, Stefanie (author)
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
Chen, Huijun (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.
Arnold, Hannah (author)
Uppsala universitet,Vaskulärbiologi
Skoczylas, Renae (author)
Uppsala universitet,Vaskulärbiologi
Bower, Neil I. (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.
Paterson, Scott (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.;Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
Lagendijk, Anne Karine (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.
Baillie, Gregory J. (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.
Leshchiner, Ignaty (author)
Harvard Med Sch, Massachusetts Gen Hosp, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
Simons, Cas (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.;Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic, Australia.
Smith, Kelly A. (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.;Univ Melbourne, Dept Anat & Physiol, Parkville, Vic, Australia.
Goessling, Wolfram (author)
Harvard Med Sch, Massachusetts Gen Hosp, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA.
Heath, Joan K. (author)
Walter & Eliza Hall Inst Med Res, Epigenet & Dev Div, Parkville, Vic, Australia.;Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia.
Pearson, Richard B. (author)
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.;Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic, Australia.;Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia.
Sanij, Elaine (author)
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.;Univ Melbourne, Dept Clin Pathol, Parkville, Vic, Australia.;St Vincents Inst Med Res, Fitzroy, Vic, Australia.
Schulte-Merker, Stefan (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.;WWU Munster, Inst Cardiovasc Organogenesis & Regenerat, Med Fac, Munster, Germany.;Hubrecht Inst KNAW, Utrecht, Netherlands.;Univ Med Ctr, Utrecht, Netherlands.
Hogan, Benjamin M. (author)
Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld, Australia.;Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.;Univ Melbourne, Dept Anat & Physiol, Parkville, Vic, Australia.;Hubrecht Inst KNAW, Utrecht, Netherlands.;Univ Med Ctr, Utrecht, Netherlands.
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 (creator_code:org_t)
2021-11-08
2021
English.
In: Nature Cell Biology. - : Springer Nature. - 1465-7392 .- 1476-4679. ; 23:11, s. 1136-1147
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Hogan and colleagues report that the RNA helicase Ddx21 mediates Vegfc-stimulated lymphangiogenesis during zebrafish development through controlling rDNA transcription and ribosome biogenesis in endothelial cells. The development of a functional vasculature requires the coordinated control of cell fate, lineage differentiation and network growth. Cellular proliferation is spatiotemporally regulated in developing vessels, but how this is orchestrated in different lineages is unknown. Here, using a zebrafish genetic screen for lymphatic-deficient mutants, we uncover a mutant for the RNA helicase Ddx21. Ddx21 cell-autonomously regulates lymphatic vessel development. An established regulator of ribosomal RNA synthesis and ribosome biogenesis, Ddx21 is enriched in sprouting venous endothelial cells in response to Vegfc-Flt4 signalling. Ddx21 function is essential for Vegfc-Flt4-driven endothelial cell proliferation. In the absence of Ddx21, endothelial cells show reduced ribosome biogenesis, p53 and p21 upregulation and cell cycle arrest that blocks lymphangiogenesis. Thus, Ddx21 coordinates the lymphatic endothelial cell response to Vegfc-Flt4 signalling by balancing ribosome biogenesis and p53 function. This mechanism may be targetable in diseases of excessive lymphangiogenesis such as cancer metastasis or lymphatic malformation.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

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