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Molecular and Cellular Biology, January 2005, p. 355-363, Vol. 25, No. 1
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.1.355-363.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Vascular Endothelial Growth Factor A (VEGF-A) Is Involved in Guidance of VEGF Receptor-Positive Cells to the Anterior Portion of Early Embryos

Sachie Hiratsuka,1,2 Yuki Kataoka,3 Kazuki Nakao,4 Kenji Nakamura,5 Shunichi Morikawa,6 Satoshi Tanaka,7 Motoya Katsuki,8 Yoshiro Maru,2 and Masabumi Shibuya1*

Department of Genetics,1 Laboratory of Gene Expression and Regulation, Institute of Medical Science,3 Laboratory of Cellular Biochemistry, Animal Resource Science/Veterinary Medical Science, University of Tokyo,7 Department of Pharmacology,2 Department of Anatomy & Developmental Biology, Tokyo Women's Medical University School of Medicine,6 Reproductive Engineering Section, Mouse Genome Technology Center, Mitsubishi Kagaku Institute of Life Science, Tokyo,5 Laboratory for Animal Resource and Genetic Engineering, RIKEN, Center for Developmental Biology, Hyogo,4 National Institute for Basic Biology, Aichi, Japan8

Received 27 June 2004/ Returned for modification 4 August 2004/ Accepted 4 October 2004

The hemangioblast in the mesoderm gives rise to both angioblasts and hematopoietic stem cells. The movement of hemangioblast precursor cells in the fetal trunk is a critical event in early embryogenesis. Vascular endothelial growth factor (VEGF) signaling is likely involved in this migration given the partial disturbance of VEGF receptor (VEGFR)-positive cell accumulation and migration in VEGFR2 null mice or mice with a truncated VEGFR1. However, it is not clear how the VEGF system regulates this migration or its direction. We show here that the expression of VEGF-A is dominant in the anterior portion of the embryo, whereas VEGFR1 and VEGFR2 are expressed in the posterior portion of the embryo. An inhibitor of VEGFR kinase blocked the migration of VEGFR-positive cells in a whole-embryo culture system. In addition, VEGFR-positive cells migrated toward a VEGFR1- or VEGFR2-specific ligand in vitro. Furthermore, VEGFR-positive cells derived from wild-type or VEGFR2+/– mice moved rapidly anteriorly, whereas cells derived from VEGFR2+/– mice carrying a truncated VEGFR1 [VEGFR1(TM-TK)–/–] migrated little when injected into wild-type mice. These results suggest that the VEGF-A protein concentrated in the anterior region plays an important role in the guidance of VEGFR-positive cells from the posterior portion to the head region by interacting with VEGFR in the mouse embryo.

* Corresponding author. Mailing address: Department of Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Phone: 81-3-5449-5550. Fax: 81-3-5449-5425. E-mail: shibuya{at}ims.u-tokyo.ac.jp.

Molecular and Cellular Biology, January 2005, p. 355-363, Vol. 25, No. 1
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.1.355-363.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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