Experimental Brain Research

, Volume 163, Issue 1, pp 86–99 | Cite as

Noggin and basic FGF were implicated in forebrain fate and caudal fate, respectively, of the neural tube-like structures emerging in mouse ES cell culture

  • Shunmei Chiba
  • Manae S. Kurokawa
  • Hideshi Yoshikawa
  • Ritsuko Ikeda
  • Mitsuhiro Takeno
  • Mamoru Tadokoro
  • Hiroaki Sekino
  • Takuo Hashimoto
  • Noboru Suzuki
Research Article


We developed neural tube-like structures accompanying neural crest-like cells by treating embryonic stem (ES) cells with retinoic acid. The structures contained pseudostratified Nestin+Vimentin+ neuroepithelial cells surrounded by Masson staining+ basement membrane. βIIItubulin+Synaptophysin+ mature neurons and glial fibrillary acidic protein (GFAP)+ glial cells dispersed outside of the membrane. Addition of Noggin to the culture induced prominent proliferation of the neuroepithelial cells, leading to epithelial hyperstratification of the structures. mRNAs of transcription factors essential for forebrain development such as Emx1/2 and Pax6 were specifically expressed and Islet1+Lim1/2- motoneurons appeared by the addition of Noggin. In contrast, basic fibroblast growth factor (bFGF) promoted enlargement of central lumen and elongation of the structures. mRNAs of caudal markers, Gbx2, Cdx2 and Hoxb4/9 were expressed and Lim1/2+ spinal motoneurons appeared by the addition of bFGF. Addition of BMP-4 similarly brought about mild enlargement of central lumen of the structures. Interestingly, the addition of BMP-4 induced Slug+ neural crest-like cells surrounding the tube-like structures. mRNAs of Snail and dHand, other markers for neural crest cells, were also expressed by the addition of BMP-4. These results suggest that Noggin lead the neural-tube like structures to forebrain fate, whereas bFGF was involved in the caudalization. BMP-4 was implicated in emergence of the neural crest-like cells. Differentiation of ES cells by the present methods may mimic neurulation and subsequent neural development of early embryos, and elucidates the opposite effects of Noggin and bFGF for the neural tube development.


bFGF Caudalization ES cell Forebrain Neural tube Neuroepithelial cell Noggin Retinoic acid 



This work was supported, in part, by a 2001 grant for the promotion of the advancement of education and research in graduate schools from the promotion and mutual aid corporation for private schools of Japan 2001 grant in aid for scientific research project No. 13037033 from the Ministry of Education, Culture, Sports, and Technology of Japan 2001 special coordination funds of the Ministry of Education, Culture, Sports, and Technology of Japan 2001 Comprehensive research on aging and health of the health science research grants of the Ministry of Health, Labor, and Welfare of Japan, and a grant from the SRF Foundation.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Shunmei Chiba
    • 1
    • 2
  • Manae S. Kurokawa
    • 1
  • Hideshi Yoshikawa
    • 1
  • Ritsuko Ikeda
    • 1
    • 2
  • Mitsuhiro Takeno
    • 1
  • Mamoru Tadokoro
    • 3
  • Hiroaki Sekino
    • 2
  • Takuo Hashimoto
    • 2
  • Noboru Suzuki
    • 1
    • 4
  1. 1.Departments of Immunology and MedicineSt. Marianna University School of MedicineMiyamae-kuJapan
  2. 2.Department of NeurosurgerySt. Marianna University School of MedicineMiyamae-kuJapan
  3. 3.Department of PathologySt. Marianna University School of MedicineMiyamae-kuJapan
  4. 4.Department of Regenerative Medicine, Institute of Advanced Medical ScienceSt. Marianna University Graduate School of MedicineMiyamae-kuJapan

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