Document Detail


The NOTCH pathway contributes to cell fate decision in myelopoiesis.
MedLine Citation:
PMID:  21933862     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Controversy persists regarding the role of Notch signaling in myelopoiesis. We have used genetic approaches, employing two Notch zebrafish mutants deadly seven (DES) and beamter (BEA) with disrupted function of notch1a and deltaC, respectively, and Notch1a morphants to analyze the development of leukocyte populations in embryonic and mature fish.
DESIGN AND METHODS: Myelomonocytes were quantified in early embryos by in situ hybridization using a myeloper-oxidase (mpx) probe. Morpholinos were used to knock down expression of Notch1a or DeltaC. Wound healing assays and/or flow cytometry were used to quantify myelomonocytes in 5-day post-fertilization (dpf) Notch mutants (BEA and DES), morphants or pu.1:GFP, mpx:GFP and fms:RFP transgenic embryos. Flow cytometry was performed on 2-3 month old mutant fish.
RESULTS: The number of mpx(+) cells in embryos was reduced at 48 hpf (but not at 26 hpf) in DES compared to WT. At 5 dpf this was reflected by a reduction in the number of myelomonocytic cells found at the wound site in mutants and in Notch1a morphants. This was due to a reduced number of myelomonocytes developing rather than a deficit in the migratory ability since transient inhibition of Notch signaling using DAPT had no effect. The early deficit in myelopoiesis was maintained into later life, 2-3 month old BEA and DES fish having a decreased proportion of myelomonocytes in both the hematopoietic organ (kidney marrow) and the periphery (coelomic cavity).
CONCLUSIONS: Our results indicate that defects in Notch signaling affect definitive hematopoiesis, altering myelopoiesis from the early stages of development into the adult.
Authors:
Laurence Bugeon; Harriet B Taylor; Fränze Progatzky; Michelle I Lin; Charles D Ellis; Natalie Welsh; Emma Smith; Neil Vargesson; Caroline Gray; Stephen A Renshaw; Timothy J A Chico; Leonard I Zon; Jonathan Lamb; Margaret J Dallman
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-20
Journal Detail:
Title:  Haematologica     Volume:  96     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-07     Completed Date:  2012-04-04     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  1753-60     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Embryo, Nonmammalian / cytology,  embryology*
Homeodomain Proteins / genetics,  metabolism*
Intracellular Signaling Peptides and Proteins / genetics,  metabolism
Membrane Proteins / genetics,  metabolism
Myelopoiesis / physiology*
Nerve Tissue Proteins / genetics,  metabolism*
Organisms, Genetically Modified / embryology,  genetics
Receptor, Notch1 / genetics,  metabolism*
Signal Transduction / physiology*
Zebrafish / embryology*,  genetics
Zebrafish Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
G0701932//Medical Research Council; PG/09/087/28051//British Heart Foundation; //Medical Research Council
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Receptor, Notch1; 0/Zebrafish Proteins; 0/delta protein; 0/notch1a protein, zebrafish
Comments/Corrections
Comment In:
Haematologica. 2011 Dec;96(12):1735-7   [PMID:  22147769 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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