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MRTF-SRF signaling is required for seeding of HSC/Ps in bone marrow during development

Costello, Patrick, Sargent, Mathew, Maurice, Diane, Esnault, Cyril, Foster, Katie, Dos Anjos Afonso, Fernando and Treisman, Richard 2015. MRTF-SRF signaling is required for seeding of HSC/Ps in bone marrow during development. Blood 125 (8) , pp. 1244-1255. 10.1182/blood-2014-08-595603

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Abstract

Chemokine signaling is important for the seeding of different sites by hematopoietic stem cells (HSCs) during development. Serum response factor (SRF) controls multiple genes governing adhesion and migration, mainly by recruiting members of the myocardin-related transcription factor (MRTF) family of G-actin–regulated cofactors. We used vav-iCre to inactivate MRTF-SRF signaling early during hematopoietic development. In both Srf- and Mrtf-deleted animals, hematopoiesis in fetal liver and spleen is intact but does not become established in fetal bone marrow. Srf-null HSC progenitor cells (HSC/Ps) fail to effectively engraft in transplantation experiments, exhibiting normal proximal signaling responses to SDF-1, but reduced adhesiveness, F-actin assembly, and reduced motility. Srf-null HSC/Ps fail to polarize in response to SDF-1 and cannot migrate through restrictive membrane pores to SDF-1 or Scf in vitro. Mrtf-null HSC/Ps were also defective in chemotactic responses to SDF-1. Srf-null HSC/Ps exhibit substantial deficits in cytoskeletal gene expression. MRTF-SRF signaling is thus critical for expression of genes required for the response to chemokine signaling during hematopoietic development

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH426 Genetics
Publisher: American Society of Hematology
ISSN: 0006-4971
Date of Acceptance: 30 December 2014
Last Modified: 15 Mar 2019 12:14
URI: http://orca.cf.ac.uk/id/eprint/82645

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