Embryonic Stem Cells/Induced Pluripotent Stem Cells

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A Role for Borg5 During Trophectoderm Differentiation†‡§

  1. Queenie P. Vong1,2,
  2. Zhonghua Liu1,2,
  3. Jae Gyu Yoo3,
  4. Rong Chen1,2,
  5. Wen Xie4,
  6. Alexei A. Sharov3,
  7. Chen-Ming Fan1,
  8. Chengyu Liu4,
  9. Minoru S.H. Ko3,
  10. Yixian Zheng1,2,¶,*

Article first published online: 15 APR 2010

DOI: 10.1002/stem.428

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 6, pages 1030–1038, June 2010

Additional Information

How to Cite

Vong, Q. P., Liu, Z., Yoo, J. G., Chen, R., Xie, W., Sharov, A. A., Fan, C.-M., Liu, C., Ko, M. S. and Zheng, Y. (2010), A Role for Borg5 During Trophectoderm Differentiation. STEM CELLS, 28: 1030–1038. doi: 10.1002/stem.428

Author Information

  1. 1

    Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland, USA

  2. 2

    Howard Hughes Medical Institute, Baltimore, Maryland, USA

  3. 3

    Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, Maryland, USA

  4. 4

    Transgenic Core Facility, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA

  1. Telephone: 410-246-3032; Fax: 410-467-1147

*Department of Embryology, Carnegie Institution for Science, Howard Hughes Medical Institute, Baltimore, MD 21218, USA

  1. †

    Author contributions: Q.P.V and Z.L. contributed equally to this work. Q.P.V., Z.L., and Y.Z.: conceived, designed the experiments, and analyzed the data; Q.P.V., Z.L., J.G.Y., R.C., and W.X.: performed experiments with advise from Y.Z., C.L., and C-M.F; A.A.S. and M.S.H.K.: contributed the microarray data and whole genome analyses; Y.Z.: wrote the manuscript with Q.P.V., Z.L., C.M.F., and C.L.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLS EXPRESS April 15, 2010.

Publication History

  1. Issue published online: 8 JUN 2010
  2. Article first published online: 15 APR 2010
  3. Accepted manuscript online: 15 APR 2010 12:00AM EST
  4. Manuscript Accepted: 26 MAR 2010
  5. Manuscript Received: 28 JAN 2010

Funded by

  • Intramural Research Program of the NIH
  • NIA
  • NHLBI
  • National Institute of Animal Science, Rural Development Administration, 250 Omokcheon-Dong, Gwonseon-Gu Suwon 441-350, Republic of Korea

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Keywords:

  • Borg5;
  • Cdx2;
  • Embryonic stem cells;
  • Trophectoderm;
  • Cell morphogenesis;
  • Transcription;
  • Differentiation

Abstract

Stem cell differentiation is accompanied by a gradual cellular morphogenesis and transcriptional changes. Identification of morphological regulators that control cell behavior during differentiation could shed light on how cell morphogenesis is coupled to transcriptional changes during development. By analyzing cellular behavior during differentiation of mouse embryonic stem cells (ESCs), we uncover a role of Borg5 (binder of Rho guanosine 5′-triphosphatase 5) in regulating trophectoderm (TE) cell morphogenesis. We report that differentiation of ESCs toward TE is accompanied by enhanced actin protrusion and cell motility that require upregulation of Borg5. Borg5 interacts with both Cdc42 and atypical protein kinase C (aPKC) and functions downstream of Cdc42 to enhance TE cell motility. Borg5 is required for the sorting of differentiating TE to the outside of ESCs in vitro. In developing embryos, Borg5 protein localizes to cell–cell contacts and the cytoplasm after compaction. It exhibits higher levels of expression in outer cells than in inner cells in morula and blastocysts. Reduction of Borg5 disrupts aPKC localization and inhibits blastocyst formation. Since Cdx2 and Borg5 facilitate each other's expression as ESCs differentiate toward TE, we propose that cell morphogenesis is coupled with transcriptional changes to regulate TE differentiation. Our studies also demonstrate the utility of ESCs in identifying morphological regulators important for development. STEM Cells 2010;28:1030–1038

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