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Journal of Biochemistry Advance Access published online on July 14, 2006
Journal of Biochemistry, doi:10.1093/jb/mvj151
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© 2006 The Japanese Biochemical Society.
Received June 7, 2006
Accepted June 15, 2006

Regular Paper

Platelet Derived Growth Factor Receptor Alpha Is Essential for Establishing a Microenvironment That Supports Definitive Erythropoiesis

Wen-Ling Li 1, Yoshihiro Yamada 2, Masaya Ueno 2, Satomi Nishikawa 3, Shin-Ichi Nishikawa 3, and Nobuyuki Takakura 4 *

1 Department of Stem Cell Biology, Cancer Research Institute of Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan
2 Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
3 Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minami-machi, Kobe, Hyogo 650-0047, Japan
4 Department of Stem Cell Biology, Cancer Research Institute of Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan; Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan

* To whom correspondence should be addressed.
Nobuyuki Takakura, E-mail: ntakaku{at}biken.osaka-u.ac.jp


  Abstract

The hematopoietic system undergoes a qualitative change during the embryogenesis of most vertebrates. It is designated as the shift of primitive to definitive hematopoiesis and suitable microenvironment must be established to support this shift.

While studying the role of platelet derived growth factor receptor {alpha} (PDGFR {alpha}) in embryonic hematopoiesis, we found that it was expressed in a stromal cell component of liver, a major site of this shift, but not in the yolk sac, the site of primitive hematopoiesis. Thus, we considered that development of PDGFR{alpha} positive stromal cells is an essential requirement for this shift. Without PDFGR{alpha} positive cell component, erythropoiesis was suppressed in the culture of fetal liver. Moreover, injection of an antagonistic anti- PDGFR{alpha} monoclonal antibody during embryogenesis suppressed the production of definitive erythrocytes. These indicated that PDGF exerts its effect on a subset of stromal components to prepare a microenvironment that can support the definitive erythropoiesis.

Keywords: PDGF; PDGFR{alpha}; erythropoiesis; erythropoietin; hematopoiesis; fetal liver.
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