Skip to main content

Advertisement

SpringerLink
Log in

Ontogeny of ramified CD45 cells in chicken embryo and their contribution to bursal secretory dendritic cells

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Embryonic tissues contain highly ramified stellate-shaped cells expressing CD45 and MHC II antigens but their origin and immunophenotype are unknown. Using staged avian embryos and cell-type-specific antibodies, we establish a detailed spatiotemporal ontogeny of cells that express CD45, the earliest marker of hematopoietic stem cells in the chick. CD45 immunostaining marks three distinct embryonic cell populations: round, ramified and amoeboid cells. The round and ramified CD45+ cells appear first in yolk-sac blood islands before the onset of circulation. A subpopulation of round cells co-expresses the thrombocyte-specific CD51/CD61 antigen. Amoeboid cells express macrophage-specific antigens and frequently occur in regions of apoptosis. Ramified cells are distributed uniformly in the embryonic mesenchyme, colonize lymphoid and non-lymphoid organs and later express MHC II. To study the origin of CD45+ cells, 2-day-old chick embryos were ablated from the yolk sac before the establishment of circulation and incubated for 2–5 days. Large numbers of CD45+MHC II+ ramified cells differentiated in the yolk sac. Yolk-sac chimeras were generated by grafting embryos into GFP-expressing de-embryonated yolk sacs. GFP/CD45 co-expressing ramified and amoeboid cells colonized all organ primordia in the donor embryo. We also recombined GFP+ yolk sac with the bursa of Fabricius and found ramified GFP+CD45+ cells in the bursa where they differentiated into dendritic cells. Thus, CD45 cells are first present in the yolk sac during primitive hematopoiesis and then migrate from the extra-embryonic yolk sac to give rise to cells throughout all organ primordia, including dendritic cells in the bursa of Fabricius.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Alliot F, Godin I, Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117:145–152

    Article  CAS  PubMed  Google Scholar 

  • Balic A, Garcia-Morales C, Vervelde L, Gilhooley H, Sherman A, Garceau V, Gutowska MW, Burt DW, Kaiser P, Hume DA, Sang HM (2014) Visualisation of chicken macrophages using transgenic reporter genes: insights into the development of the avian macrophage lineage. Development 141:3255–3265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bollerot K, Romero S, Dunon D, Jaffredo T (2005) Core binding factor in the early avian embryo: cloning of Cbfbeta and combinatorial expression patterns with Runx1. Gene Expr Patterns 6:29–39

    Article  CAS  PubMed  Google Scholar 

  • Caprioli A, Minko K, Drevon C, Eichmann A, Dieterlen-Lievre F, Jaffredo T (2001) Hemangioblast commitment in the avian allantois: cellular and molecular aspects. Dev Biol 238:64–78

    Article  CAS  PubMed  Google Scholar 

  • Chen CH, Chanh TC, Cooper MD (1984) Chicken thymocyte-specific antigen identified by monoclonal antibodies: ontogeny, tissue distribution and biochemical characterization. Eur J Immunol 14:385–391

    Article  CAS  PubMed  Google Scholar 

  • Corbel C (2002) Expression of alphaVbeta3 integrin in the chick embryo aortic endothelium. Int J Dev Biol 46:827–830

    CAS  PubMed  Google Scholar 

  • Corbel C, Lehmann A, Davison F (2000) Expression of CD44 during early development of the chick embryo. Mech Dev 96:111–114

    Article  CAS  PubMed  Google Scholar 

  • Corbel C, Vaigot P, Salaun J (2005) (alpha)IIb Integrin, a novel marker for hemopoietic progenitor cells. Int J Dev Biol 49:279–284

    Article  CAS  PubMed  Google Scholar 

  • Cormier F (1993) Avian pluripotent haemopoietic progenitor cells: detection and enrichment from the para-aortic region of the early embryo. J Cell Sci 105:661–666

    PubMed  Google Scholar 

  • Cormier F, Dieterlen-Lievre F (1988) The wall of the chick embryo aorta harbours M-CFC, G-CFC, GM-CFC and BFU-E. Development 102:279–285

    CAS  PubMed  Google Scholar 

  • Cuadros MA, Coltey P, Carmen Nieto M, Martin C (1992) Demonstration of a phagocytic cell system belonging to the hemopoietic lineage and originating from the yolk sac in the early avian embryo. Development 115:157–168

    CAS  PubMed  Google Scholar 

  • Cuadros MA, Santos AM, Martin-Oliva D, Calvente R, Tassi M, Marin-Teva JL, Navascues J (2006) Specific immunolabeling of brain macrophages and microglial cells in the developing and mature chick central nervous system. J Histochem Cytochem 54:727–738

    Article  CAS  PubMed  Google Scholar 

  • Dieterlen-Lievre F (1975) On the origin of haemopoietic stem cells in the avian embryo: an experimental approach. J Embryol Exp Morphol 33:607–619

    CAS  PubMed  Google Scholar 

  • Dieterlen-Lievre F, Martin C (1981) Diffuse intraembryonic hemopoiesis in normal and chimeric avian development. Dev Biol 88:180–191

    Article  CAS  PubMed  Google Scholar 

  • Dieterlen-Lievre F, Beaupain D, Martin C (1976) Origin of erythropoietic stem cells in avian development: shift from the yolk sac to an intraembryonic site. Ann Immunol (Paris) 127:857–863

    CAS  Google Scholar 

  • Garceau V, Balic A, Garcia-Morales C, Sauter KA, McGrew MJ, Smith J, Vervelde L, Sherman A, Fuller TE, Oliphant T, Shelley JA, Tiwari R, Wilson TL, Chintoan-Uta C, Burt DW, Stevens MP, Sang HM, Hume DA (2015) The development and maintenance of the mononuclear phagocyte system of the chick is controlled by signals from the macrophage colony-stimulating factor receptor. BMC Biol 13:12

    Article  PubMed  PubMed Central  Google Scholar 

  • Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Godin I, Cumano A (2005) Of birds and mice: hematopoietic stem cell development. Int J Dev Biol 49:251–257

    Article  CAS  PubMed  Google Scholar 

  • Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, Garner H, Trouillet C, Bruijn MF de, Geissmann F, Rodewald HR (2015) Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 518:547–551

  • Guillemot FP, Oliver PD, Peault BM, Le Douarin NM (1984) Cells expressing Ia antigens in the avian thymus. J Exp Med 160:1803–1819

    Article  CAS  PubMed  Google Scholar 

  • Hamburger V, Hamilton HL (1992) A series of normal stages in the development of the chick embryo. 1951. Dev Dyn 195:231–272

    Article  CAS  PubMed  Google Scholar 

  • Hoeffel G, Chen J, Lavin Y, Low D, Almeida FF, See P, Beaudin AE, Lum J, Low I, Forsberg EC, Poidinger M, Zolezzi F, Larbi A, Ng LG, Chan JK, Greter M, Becher B, Samokhvalov IM, Merad M, Ginhoux F (2015) C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42:665–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Houssaint E, Diez E, Pink JR (1987) Ontogeny and tissue distribution of the chicken Bu-1a antigen. Immunology 62:463–470

    CAS  PubMed  PubMed Central  Google Scholar 

  • Houssaint E, Mansikka A, Vainio O (1991) Early separation of B and T lymphocyte precursors in chick embryo. J Exp Med 174:397–406

    Article  CAS  PubMed  Google Scholar 

  • Igyártó BZ, Lackó E, Oláh I, Magyar A (2006) Characterization of chicken epidermal dendritic cells. Immunology 119:278–288

    Article  PubMed  PubMed Central  Google Scholar 

  • Igyártó BZ, Magyar A, Oláh I (2007) Origin of follicular dendritic cell in the chicken spleen. Cell Tissue Res 327:83–92

    Article  PubMed  Google Scholar 

  • Igyártó BZ, Nagy N, Magyar A, Oláh I (2008) Identification of the avian B-cell-specific Bu-1 alloantigen by a novel monoclonal antibody. Poult Sci 87:351–355

    Article  PubMed  Google Scholar 

  • Jaffredo T, Gautier R, Eichmann A, Dieterlen-Lievre F (1998) Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny. Development 125:4575–4583

    CAS  PubMed  Google Scholar 

  • Jaffredo T, Gautier R, Brajeul V, Dieterlen-Lievre F (2000) Tracing the progeny of the aortic hemangioblast in the avian embryo. Dev Biol 224:204–214

    Article  CAS  PubMed  Google Scholar 

  • Jeurissen SH, Claassen E, Janse EM (1992) Histological and functional differentiation of non-lymphoid cells in the chicken spleen. Immunology 77:75–80

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jotereau FV, Houssaint E (1977) Experimental studies on the migration and differentiation of primary lymphoid stem cells in the avian embryo. In: Solomon JB, Horton JD (eds) Developmental immunobiology. Elsevier/North-Holland, Amsterdam, pp 123–130

    Google Scholar 

  • Katevuo K, Imhof BA, Boyd R, Chidgey A, Bean A, Dunon D, Gobel TW, Vainio O (1999) ChT1, an Ig superfamily molecule required for T cell differentiation. J Immunol 162:5685–5694

    CAS  PubMed  Google Scholar 

  • Kurz H, Christ B (1998) Embryonic CNS macrophages and microglia do not stem from circulating, but from extravascular precursors. Glia 22:98–102

    Article  CAS  PubMed  Google Scholar 

  • Kurz H, Korn J, Eggli PS, Huang R, Christ B (2001) Embryonic central nervous system angiogenesis does not involve blood-borne endothelial progenitors. J Comp Neurol 436:263–274

    Article  CAS  PubMed  Google Scholar 

  • Lampisuo M, Liippo J, Vainio O, McNagny KM, Kulmala J, Lassila O (1999) Characterization of prethymic progenitors within the chicken embryo. Int Immunol 11:63–69

    Article  CAS  PubMed  Google Scholar 

  • LaRue AC, Lansford R, Drake CJ (2003) Circulating blood island-derived cells contribute to vasculogenesis in the embryo proper. Dev Biol 262:162–172

    Article  CAS  PubMed  Google Scholar 

  • Lippincott-Schwartz J, Fambrough DM (1986) Lysosomal membrane dynamics: structure and interorganellar movement of a major lysosomal membrane glycoprotein. J Cell Biol 102:1593–1605

    Article  CAS  PubMed  Google Scholar 

  • Manaia A, Lemarchandel V, Klaine M, Max-Audit I, Romeo P, Dieterlen-Lievre F, Godin I (2000) Lmo2 and GATA-3 associated expression in intraembryonic hemogenic sites. Development 127:643–653

    CAS  PubMed  Google Scholar 

  • Martin C, Beaupain D, Dieterlen-Lievre F (1978) Developmental relationships between vitelline and intra-embryonic haemopoiesis studied in avian “yolk sac chimaeras”. Cell Differ 7:115–130

    Article  CAS  PubMed  Google Scholar 

  • Masteller EL, Larsen RD, Carlson LM, Pickel JM, Nickoloff B, Lowe J, Thompson CB, Lee KP (1995) Chicken B cells undergo discrete developmental changes in surface carbohydrate structure that appear to play a role in directing lymphocyte migration during embryogenesis. Development 121:1657–1667

    CAS  PubMed  Google Scholar 

  • McGrew MJ, Sherman A, Ellard FM, Lillico SG, Gilhooley HJ, Kingsman AJ, Mitrophanous KA, Sang H (2004) Efficient production of germline transgenic chickens using lentiviral vectors. EMBO Rep 5:728–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McIntyre BA, Alev C, Tarui H, Jakt LM, Sheng G (2008) Expression profiling of circulating non-red blood cells in embryonic blood. BMC Dev Biol 8:21

    Article  PubMed  PubMed Central  Google Scholar 

  • McNagny KM, Lim F, Grieser S, Graf T (1992) Cell surface proteins of chicken hematopoietic progenitors, thrombocytes and eosinophils detected by novel monoclonal antibodies. Leukemia 6:975–984

    CAS  PubMed  Google Scholar 

  • Minko K, Bollerot K, Drevon C, Hallais MF, Jaffredo T (2003) From mesoderm to blood islands: patterns of key molecules during yolk sac erythropoiesis. Gene Expr Patterns 3:261–272

    Article  CAS  PubMed  Google Scholar 

  • Nagy N, Goldstein AM (2006) Intestinal coelomic transplants: a novel method for studying enteric nervous system development. Cell Tissue Res 326:43–55

    Article  PubMed  Google Scholar 

  • Nagy N, Olah I (2010) Experimental evidence for the ectodermal origin of the epithelial anlage of the chicken bursa of Fabricius. Development 137:3019–3023

    Article  CAS  PubMed  Google Scholar 

  • Nagy N, Magyar A, Toth M, Olah I (2004) Origin of the bursal secretory dendritic cell. Anat Embryol (Berl) 208:97–107

    Article  CAS  Google Scholar 

  • Nagy N, Biro E, Takacs A, Polos M, Magyar A, Olah I (2005) Peripheral blood fibrocytes contribute to the formation of the avian spleen. Dev Dyn 232:55–66

    Article  PubMed  Google Scholar 

  • Nagy N, Bodi I, Olah I (2016a) Avian dendritic cells: phenotype and ontogeny in lymphoid organs. Dev Comp Immunol 58:47–59

    Article  CAS  PubMed  Google Scholar 

  • Nagy N, Barad C, Graham HK, Hotta R, Cheng LS, Fejszak N, Goldstein AM (2016b) Sonic hedgehog controls enteric nervous system development by patterning the extracellular matrix. Development 143:264–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakazawa F, Nagai H, Shin M, Sheng G (2006) Negative regulation of primitive hematopoiesis by the FGF signaling pathway. Blood 108:3335–3343

    Article  CAS  PubMed  Google Scholar 

  • Ody C, Vaigot P, Quere P, Imhof BA, Corbel C (1999) Glycoprotein IIb-IIIa is expressed on avian multilineage hematopoietic progenitor cells. Blood 93:2898–2906

    CAS  PubMed  Google Scholar 

  • Olah I, Nagy N (2013) Retrospection to discovery of bursal function and recognition of avian dendritic cells; past and present. Dev Comp Immunol 41:310–315

    Article  CAS  PubMed  Google Scholar 

  • Pardanaud L, Eichmann A (2006) Identification, emergence and mobilization of circulating endothelial cells or progenitors in the embryo. Development 133:2527–2537

    Article  CAS  PubMed  Google Scholar 

  • Pardanaud L, Eichmann A (2011) Extraembryonic origin of circulating endothelial cells. PLoS One 6:e25889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perdiguero EG, Klapproth K, Schulz C, Busch K, Bruijn M de, Rodewald HR, Geissmann F (2015) The origin of tissue-resident macrophages: when an erythro-myeloid progenitor is an erythro-myeloid progenitor. Immunity 43:1023–1024

  • Pharr T, Olah I, Bricker J, Olson WC, Ewert D, Marsh J, Glick B (1995) Characterization of a novel monoclonal antibody, EIV-E12, raised against enriched splenic ellipsoid-associated cells. Hybridoma 14:51–57

    Article  CAS  PubMed  Google Scholar 

  • Saynajakangas R, Uchida T, Vainio O (2009) Differential gene expression in CD45 cells at para-aortic foci stage of chicken haematopoiesis. Scand J Immunol 70:288–294

    Article  CAS  PubMed  Google Scholar 

  • Sheng G (2010) Primitive and definitive erythropoiesis in the yolk sac: a bird’s eye view. Int J Dev Biol 54:1033–1043

    Article  CAS  PubMed  Google Scholar 

  • Sinka L, Biasch K, Khazaal I, Peault B, Tavian M (2012) Angiotensin-converting enzyme (CD143) specifies emerging lympho-hematopoietic progenitors in the human embryo. Blood 119:3712–3723

    Article  CAS  PubMed  Google Scholar 

  • Staines K, Hunt LG, Young JR, Butter C (2014) Evolution of an expanded mannose receptor gene family. PLoS One 9:e110330

    Article  PubMed  PubMed Central  Google Scholar 

  • Tavian M, Biasch K, Sinka L, Vallet J, Peault B (2010) Embryonic origin of human hematopoiesis. Int J Dev Biol 54:1061–1065

    Article  PubMed  Google Scholar 

  • Thomas JL, Pourquie O, Coltey M, Vaigot P, Le Douarin NM (1993) Identification in the chicken of GRL1 and GRL2: two granule proteins expressed on the surface of activated leukocytes. Exp Cell Res 204:156–166

    Article  CAS  PubMed  Google Scholar 

  • Viertlboeck BC, Göbel TW (2007) Chicken thrombocytes express the CD51/CD61 integrin. Vet Immunol Immunopathol 119:137–141

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki S, Nobuhisa I, Ramadan A, Taga T (2011) Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression. Dev Growth Differ 53:870–877

    Article  CAS  PubMed  Google Scholar 

  • Yassine F, Fedecka-Bruner B, Dieterlen-Lievre F (1989) Ontogeny of the chick embryo spleen—a cytological study. Cell Differ Dev 27:29–45

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financed by the Hungarian Scientific Research Fund (OTKA): K-69061. Nándor Nagy is supported by a Bolyai Fellowship of the Hungarian Academy of Sciences. The authors thank Edit Orbán, Adrien Kovács and Orsolya Fölker for laboratory assistance. Several monoclonal antibodies in Table 1 were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by University of Iowa, Dept of Biological Sciences, Iowa City, IA 52242, USA.

Author information

Authors and Affiliations

  1. Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 58 Tűzoltó Street, Budapest, 1094, Hungary

    Dávid Dóra, Nóra Fejszák, Krisztina Minkó & Nándor Nagy

  2. Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA

    Allan M. Goldstein & Nándor Nagy

Authors
  1. Dávid Dóra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nóra Fejszák
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Allan M. Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Krisztina Minkó
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nándor Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nándor Nagy.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

This article is dedicated to Prof. Imre Oláh for his leading contribution in the field of avian dendritic cell biology.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dóra, D., Fejszák, N., Goldstein, A.M. et al. Ontogeny of ramified CD45 cells in chicken embryo and their contribution to bursal secretory dendritic cells. Cell Tissue Res 368, 353–370 (2017). https://doi.org/10.1007/s00441-017-2595-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-017-2595-y

Keywords

Search

Navigation