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Brief Communication
Nature Neuroscience  8, 855 - 857 (2005)
Published online: 5 June 2005; | doi:10.1038/nn1485

Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia

Takaharu Taketomi1, 2, Daigo Yoshiga1, 2, Koji Taniguchi1, Takashi Kobayashi1, Atsushi Nonami1, Reiko Kato1, Mika Sasaki1, Atsuo Sasaki1, Hitoshi Ishibashi3, Maiko Moriyama4, Kei-ichiro Nakamura5, Junji Nishimura6 & Akihiko Yoshimura1

1  Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

2  Division of Oral and Maxillofacial Oncology, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

3  Department of Physiology, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

4  Department of Anesthesiology, Kurume University School of Medicine, Asahimachi, Kurume 830-0011, Japan.

5  Department of Anatomy, Kurume University School of Medicine, Asahimachi, Kurume 830-0011, Japan.

6  Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Correspondence should be addressed to Akihiko Yoshimura yakihiko@bioreg.kyushu-u.ac.jp
We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction. Glial cell line−derived neurotrophic factor (GDNF) induced hyperactivation of ERK and Akt in enteric nerve cells. Anti-GDNF antibody administration corrected nerve hyperplasia in Sprouty2-deficient mice. We show Sprouty2 to be a negative regulator of GDNF for the neonatal development or survival of enteric nerve cells.


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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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