Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos - PubMed

Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos

Martin Gering et al. Dev Cell. 2005 Mar.

Free article

Abstract

Studies with embryonic explants and embryonic stem cells have suggested a role for Hedgehog (Hh) signaling in hematopoiesis. However, targeted deletion of Hh pathway components in the mouse has so far failed to provide in vivo evidence. Here we show that zebrafish embryos mutant in the Hh pathway or treated with the Hh signaling inhibitor cyclopamine display defects in adult hematopoietic stem cell (HSC) formation but not in primitive hematopoiesis. Hh is required in the trunk at three consecutive stages during vascular development: for the medial migration of endothelial progenitors of the dorsal aorta (DA), for arterial gene expression, and for the formation of intersomitic vessel sprouts. Interference with Hh signaling during the first two stages also interferes with HSC formation. Furthermore, HSC and DA formation also share Vegf and Notch requirements, which further distinguishes them from primitive hematopoiesis and underlines their close relationship during vertebrate development.

Similar articles

• Hedgehog signaling is required for differentiation of endocardial progenitors in zebrafish.

  Wong KS, Rehn K, Palencia-Desai S, Kohli V, Hunter W, Uhl JD, Rost MS, Sumanas S. Wong KS, et al. Dev Biol. 2012 Jan 15;361(2):377-91. doi: 10.1016/j.ydbio.2011.11.004. Epub 2011 Nov 12. Dev Biol. 2012. PMID: 22119054

• Signaling axis involving Hedgehog, Notch, and Scl promotes the embryonic endothelial-to-hematopoietic transition.

  Kim PG, Albacker CE, Lu YF, Jang IH, Lim Y, Heffner GC, Arora N, Bowman TV, Lin MI, Lensch MW, De Los Angeles A, Zon LI, Loewer S, Daley GQ. Kim PG, et al. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):E141-50. doi: 10.1073/pnas.1214361110. Epub 2012 Dec 12. Proc Natl Acad Sci U S A. 2013. PMID: 23236128 Free PMC article.

• Hedgehog and Bmp polarize hematopoietic stem cell emergence in the zebrafish dorsal aorta.

  Wilkinson RN, Pouget C, Gering M, Russell AJ, Davies SG, Kimelman D, Patient R. Wilkinson RN, et al. Dev Cell. 2009 Jun;16(6):909-16. doi: 10.1016/j.devcel.2009.04.014. Dev Cell. 2009. PMID: 19531361 Free PMC article.

• Molecular regulation of embryonic hematopoiesis and vascular development: a novel pathway.

  Baron MH. Baron MH. J Hematother Stem Cell Res. 2001 Oct;10(5):587-94. doi: 10.1089/152581601753193797. J Hematother Stem Cell Res. 2001. PMID: 11672504 Review.

• Developmental biology informs cancer: the emerging role of the hedgehog signaling pathway in upper gastrointestinal cancers.

  Xie K, Abbruzzese JL. Xie K, et al. Cancer Cell. 2003 Oct;4(4):245-7. doi: 10.1016/s1535-6108(03)00246-0. Cancer Cell. 2003. PMID: 14585350 Review.

Cited by

• The role of the haematopoietic stem cell niche in development and ageing.

  Cain TL, Derecka M, McKinney-Freeman S. Cain TL, et al. Nat Rev Mol Cell Biol. 2025 Jan;26(1):32-50. doi: 10.1038/s41580-024-00770-8. Epub 2024 Sep 10. Nat Rev Mol Cell Biol. 2025. PMID: 39256623 Review.

• Regulation of murine normal and stress-induced erythropoiesis by Desert Hedgehog.

  Lau CI, Outram SV, Saldaña JI, Furmanski AL, Dessens JT, Crompton T. Lau CI, et al. Blood. 2012 May 17;119(20):4741-51. doi: 10.1182/blood-2011-10-387266. Epub 2012 Mar 28. Blood. 2012. PMID: 22461491 Free PMC article.

• Modulation of WNT, Activin/Nodal and MAPK Signaling Pathways Increases Arterial Hemogenic Endothelium and Hematopoietic Stem/Progenitor Cell Formation During Human iPSC Differentiation.

  Li Y, Ding J, Araki D, Zou J, Larochelle A. Li Y, et al. bioRxiv [Preprint]. 2023 Feb 21:2023.02.21.529379. doi: 10.1101/2023.02.21.529379. bioRxiv. 2023. PMID: 36865308 Free PMC article. Updated. Preprint.

• Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation.

  Wang C, Faloon PW, Tan Z, Lv Y, Zhang P, Ge Y, Deng H, Xiong JW. Wang C, et al. Blood. 2007 Nov 15;110(10):3601-9. doi: 10.1182/blood-2007-04-086827. Epub 2007 Aug 3. Blood. 2007. PMID: 17675553 Free PMC article.

• Notch signaling distinguishes 2 waves of definitive hematopoiesis in the zebrafish embryo.

  Bertrand JY, Cisson JL, Stachura DL, Traver D. Bertrand JY, et al. Blood. 2010 Apr 8;115(14):2777-83. doi: 10.1182/blood-2009-09-244590. Epub 2010 Jan 27. Blood. 2010. PMID: 20107232 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • Gene Ontology
  • ZFIN