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

Taketomi, Takaharu; Yoshiga, Daigo; Taniguchi, Koji; Kobayashi, Takashi; Nonami, Atsushi; Kato, Reiko; Sasaki, Mika; Sasaki, Atsuo T.; Ishibashi, Hiroyuki; Moriyama, Maiko; Nakamura, Kei; Nishimura, Junji; Yoshimura, Akihiko

doi:10.1038/nn1485

Cited by 126 publications

(107 citation statements)

References 10 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…T Ayada et al bud-derived epithelial tubes (Basson et al, 2005(Basson et al, , 2006, mSprouty2 regulates embryonic lung branching morphogenesis (Tefft et al, 1999) as well as motor nerve networks in digestive organs (Taketomi et al, 2005). Angiogenesis is another form of branching morphogenesis and the overexpression of mSprouty4 has been shown to inhibit branching and sprouting of small vessels (Lee et al, 2001).…”

Section: Sprouty4 Inhibits Pip 2 Hydrolysismentioning

confidence: 99%

“…It is notable that enteric nerve development is regulated by GDNF and endothelin-3 (Angrist et al, 1996;Hempstead, 2004). Therefore, the enteric nerve dysplasia phenotype of Sprouty2 KO mice may be partly explained by hypersignaling of ET-3 (Taketomi et al, 2005). As the physiological role of GPCR ligand-induced PIP 2 hydrolysis has not been well characterized, Sprouty KO mice could be a useful tool for defining this.…”

Section: Sprouty4 Inhibits Pip 2 Hydrolysis T Ayada Et Almentioning

confidence: 99%

See 1 more Smart Citation

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

et al. 2009

View full text Add to dashboard Cite

Section: Sprouty4 Inhibits Pip 2 Hydrolysismentioning

confidence: 99%

Section: Sprouty4 Inhibits Pip 2 Hydrolysis T Ayada Et Almentioning

confidence: 99%

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

et al. 2009

View full text Add to dashboard Cite

“…Also, FGF2 (basic FGF) is an essential component of the culture media used to stimulate growth of both ENS progenitor cells and neural stem cells in vitro and maintains cells in a continuously expanding state (29,38). Finally, the mice mutant for the FGF receptor antagonist Sprouty2 exhibits ENS hyperganglionosis (39). Taken together, these findings suggest roles for FGFs in ENS development, which remain to be explored.…”

Section: Sox2 As a Potential Marker Of Proliferative And Stem Cell Pomentioning

confidence: 99%

Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes

Heanue

Pachnis

2006

Proc. Natl. Acad. Sci. U.S.A.

106

121

View full text Add to dashboard Cite

The enteric nervous system (ENS) is composed of neurons and glial cells, organized as interconnected ganglia within the gut wall, which controls persistalsis of the gut wall and secretions from its glands. The Ret receptor tyrosine kinase is expressed throughout enteric neurogenesis and is required for normal ENS development; humans with mutations in the RET locus have Hirschsprung disease (HSCR, an absence of ganglia in the colon), and mice lacking Ret have total intestinal aganglionosis. The Ret mutant mouse provides a tool for identifying genes implicated in development of the ENS. By using RNA from WT and Ret mutant (aganglionic) gut tissue and DNA microarrays, we have conducted a differential screen for ENS-expressed genes and have identified hundreds of candidate ENS-expressed genes. Forty-seven genes were selected for further analysis, representing diverse functional classes. We show that all of the analyzed genes are expressed in the ENS and that the screen was sensitive enough to identify genes marking only subpopulations of ENS cells. Our screen, therefore, was reliable and sensitive and has identified many previously undescribed genes for studying ENS development. Moreover, two of the genes identified in our screen Arhgef3 and Ctnnal1, have human homologues that map to previously identified HSCR susceptibility loci, thus representing excellent candidates for HSCR genes. This comprehensive profile of ENS gene expression refines our understanding of ENS development and serves as a resource for future developmental, biochemical, and human genetic studies.T he enteric nervous system (ENS) is composed of a vast number of neurons and glial cells, which form interconnected ganglia that control the contractility of the smooth muscle of the gut wall and the secretory activity of its glands (1). The ENS is derived from vagal and sacral enteric neural crest cells (ENCs), which invade the foregut and hindgut, respectively (2, 3). Once situated within the gut, ENCs migrate along the developing bowel, proliferate, and differentiate to form many different neuronal subtypes and make synaptic connections (4, 5). Migration of ENCs within the gut requires signaling between these cells and the gut environment and depends on dynamic changes in cell shape and adhesive properties. How cell shape and adhesion are controlled to allow regulated and directed migration of ENCs currently is unknown. Furthermore, how cell fate decisions are controlled to specify the correct number and subtypes of neurons and glial cells within ENS ganglia or how correct synaptic circuits are established also is unknown.Genetic studies in mouse and human have identified several genes whose function is required for normal ENS development (6, 7). For example, the Ret receptor tyrosine kinase is expressed in ENCs during migration into the gut and persists during later ENS development (8). Humans carrying mutations in RET develop congenital megacolon [Hirschsprung disease (HSCR) OMIM 142623; ref. 7], which is characterized by the absence of enteric ga...

show abstract

“…Furthermore, overexpression studies have revealed that cells expressing Spry proteins exhibit reduced migration, proliferation, invasion, and differentiation (15, 19, 26 -31). Recent reports, including murine knock-out studies of Spry1 and Spry2, have demonstrated that Spry proteins not only attenuate FGF-and EGF-mediated p42/44 ERK activation, but also inhibit signaling induced by glial cell line-derived neurotrophic growth factor, c-kit, insulin, platelet-derived growth factor, nerve growth factor, hepatocyte growth factor, and vascular endothelial growth factor (VEGF) (19,29,(32)(33)(34)(35)(36)(37).…”

mentioning

confidence: 99%

A Functional Interaction between Sprouty Proteins and Caveolin-1

Cabrita¹,

Jäggi

Widjaja

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Growth factor-mediated signal transduction cascades can be regulated spatio-temporally by signaling modulators, such as Sprouty proteins. The four mammalian Sprouty family members are palmitoylated phosphoproteins that can attenuate or potentiate numerous growth factor-induced signaling pathways. Previously, we have shown that Sprouty-1 and Sprouty-2 associate with Caveolin-1, the major structural protein of caveolae. Like Sprouty, Caveolin-1 inhibits growth factor-induced mitogen-activated protein kinase activation. Here, we demonstrate that all four mammalian Sprouty family members physically interact with Caveolin-1. The C terminus of Caveolin-1 is the major Sprouty-binding site, whereas Sprouty binds Caveolin-1 via its conserved C-terminal domain. A single point mutation in this domain results in loss of Caveolin-1 interaction. Moreover, we demonstrate that the various Sprouty isoforms differ dramatically in their cooperation with Caveolin-1-mediated inhibition of mitogen-activated protein kinase activation and that such cooperation is also highly dependent on the type of growth factor investigated and on cell density. Together, the data suggest that the Sprouty/Caveolin-1 interaction modulates signaling in a growth factor-and Sprouty isoform-specific manner.

show abstract

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

Cited by 126 publications

References 10 publications

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes

A Functional Interaction between Sprouty Proteins and Caveolin-1

Contact Info

Product

Resources

About