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The NOTCH pathway contributes to cell fate decision in myelopoiesis.
Haematologica. 2011 Dec; 96(12):1753-60.H

Abstract

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+Show Affiliations

Imperial College London, London, SW7 2AZ, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21933862

Citation

Bugeon, Laurence, et al. "The NOTCH Pathway Contributes to Cell Fate Decision in Myelopoiesis." Haematologica, vol. 96, no. 12, 2011, pp. 1753-60.
Bugeon L, Taylor HB, Progatzky F, et al. The NOTCH pathway contributes to cell fate decision in myelopoiesis. Haematologica. 2011;96(12):1753-60.
Bugeon, L., Taylor, H. B., Progatzky, F., Lin, M. I., Ellis, C. D., Welsh, N., Smith, E., Vargesson, N., Gray, C., Renshaw, S. A., Chico, T. J., Zon, L. I., Lamb, J., & Dallman, M. J. (2011). The NOTCH pathway contributes to cell fate decision in myelopoiesis. Haematologica, 96(12), 1753-60. https://doi.org/10.3324/haematol.2011.044115
Bugeon L, et al. The NOTCH Pathway Contributes to Cell Fate Decision in Myelopoiesis. Haematologica. 2011;96(12):1753-60. PubMed PMID: 21933862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The NOTCH pathway contributes to cell fate decision in myelopoiesis. AU - Bugeon,Laurence, AU - Taylor,Harriet B, AU - Progatzky,Fränze, AU - Lin,Michelle I, AU - Ellis,Charles D, AU - Welsh,Natalie, AU - Smith,Emma, AU - Vargesson,Neil, AU - Gray,Caroline, AU - Renshaw,Stephen A, AU - Chico,Timothy J A, AU - Zon,Leonard I, AU - Lamb,Jonathan, AU - Dallman,Margaret J, Y1 - 2011/09/20/ PY - 2011/9/22/entrez PY - 2011/9/22/pubmed PY - 2012/4/5/medline SP - 1753 EP - 60 JF - Haematologica JO - Haematologica VL - 96 IS - 12 N2 - 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. SN - 1592-8721 UR - https://www.unboundmedicine.com/medline/citation/21933862/The_NOTCH_pathway_contributes_to_cell_fate_decision_in_myelopoiesis_ L2 - http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=21933862 DB - PRIME DP - Unbound Medicine ER -