Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice

Rieko Miyamoto, Mayumi Jijiwa, Masato Asai, Kumi Kawai, Maki Ishida-Takagishi, Shinji Mii, Naoya Asai, Atsushi Enomoto, Yoshiki Murakumo, Akihiko Yoshimura, Masahide Takahashi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The glial cell line-derived neurotrophic factor (GDNF)/RET tyrosine kinase signaling pathway plays crucial roles in the development of the enteric nervous system (ENS) and the kidney. Tyrosine 1062 (Y1062) in RET is an autophosphorylation residue that is responsible for the activation of the PI3K/AKT and RAS/MAPK signaling pathways. Mice lacking signaling via Ret Y1062 show renal hypoplasia and hypoganglionosis of the ENS although the phenotype is milder than the Gdnf- or Ret-deficient mice. Sprouty2 (Spry2) was found to be an antagonist for fibroblast growth factor receptor (FGFR) and acts as an inhibitory regulator of ERK activation. Spry2-deficient mice exhibit hearing loss and enteric nerve hyperplasia. In the present study, we generated Spry2-deficient and Ret Y1062F knock-in (tyrosine 1062 is replaced with phenylalanine) double mutant mice to see if abnormalities of the ENS and kidney, caused by loss of signaling via Ret Y1062, are rescued by a deficiency of Spry2. Double mutant mice showed significant recovery of ureteric bud branching and ENS development in the stomach. These results indicate that Spry2 regulates downstream signaling mediated by GDNF/RET signaling complex in vivo.

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalDevelopmental Biology
Volume349
Issue number2
DOIs
Publication statusPublished - 2011 Jan 15

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Keywords

  • Enteric nervous system
  • RET tyrosine kinase
  • Signal transduction
  • Sprouty2
  • Ureteric bud branching

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Miyamoto, R., Jijiwa, M., Asai, M., Kawai, K., Ishida-Takagishi, M., Mii, S., Asai, N., Enomoto, A., Murakumo, Y., Yoshimura, A., & Takahashi, M. (2011). Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice. Developmental Biology, 349(2), 160-168. https://doi.org/10.1016/j.ydbio.2010.11.002