Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction

M. Albert Basson; Simge Akbulut; Judy Watson-Johnson; Ruth Simon; Thomas J. Carroll; Reena Shakya; Isabelle Gross; Gail R. Martin; Thomas Lufkin; Andrew P. McMahon; Patricia D. Wilson; Frank D. Costantini; Ivor J. Mason; Jonathan D. Licht

doi:10.1016/j.devcel.2004.12.004

Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction

M. Albert Basson, Simge Akbulut, Judy Watson-Johnson, Ruth Simon, Thomas J. Carroll, Reena Shakya, Isabelle Gross, Gail R. Martin, Thomas Lufkin, Andrew P. McMahon, Patricia D. Wilson, Frank D. Costantini, Ivor J. Mason, Jonathan D. Licht

Research output: Contribution to journal › Article › peer-review

310 Scopus citations

Abstract

Intercellular signaling molecules and their receptors, whose expression must be tightly regulated in time and space, coordinate organogenesis. Regulators of intracellular signaling pathways provide an additional level of control. Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice. Spry1^-/- embryos have supernumerary ureteric buds, resulting in the development of multiple ureters and multiplex kidneys. These defects are due to increased sensitivity of the Wolffian duct to GDNF/RET signaling, and reducing Gdnf gene dosage correspondingly rescues the Spry1 null phenotype. We conclude that the function of Spry1 is to modulate GDNF/RET signaling in the Wolffian duct, ensuring that kidney induction is restricted to a single site. These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations.

Original language	English (US)
Pages (from-to)	229-239
Number of pages	11
Journal	Developmental cell
Volume	8
Issue number	2
DOIs	https://doi.org/10.1016/j.devcel.2004.12.004
State	Published - Feb 2005

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2004.12.004

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@article{89ec2721b2bc417f8ea4da4bea3d4331,

title = "Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction",

abstract = "Intercellular signaling molecules and their receptors, whose expression must be tightly regulated in time and space, coordinate organogenesis. Regulators of intracellular signaling pathways provide an additional level of control. Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice. Spry1-/- embryos have supernumerary ureteric buds, resulting in the development of multiple ureters and multiplex kidneys. These defects are due to increased sensitivity of the Wolffian duct to GDNF/RET signaling, and reducing Gdnf gene dosage correspondingly rescues the Spry1 null phenotype. We conclude that the function of Spry1 is to modulate GDNF/RET signaling in the Wolffian duct, ensuring that kidney induction is restricted to a single site. These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations.",

author = "Basson, {M. Albert} and Simge Akbulut and Judy Watson-Johnson and Ruth Simon and Carroll, {Thomas J.} and Reena Shakya and Isabelle Gross and Martin, {Gail R.} and Thomas Lufkin and McMahon, {Andrew P.} and Wilson, {Patricia D.} and Costantini, {Frank D.} and Mason, {Ivor J.} and Licht, {Jonathan D.}",

note = "Funding Information: We thank Kevin Kelly for blastocyst injections, Uta Grieshammer for in situ probes and insightful comments on the manuscript, Debra Morrison for initial characterization of the Spry1 BAC clones, Vivette d{\textquoteright}Agati, Adrian Woolf, Francesca Cole, Debbie Hyink, Imelda McGonnel, and Clemens Kiecker for helpful advice, and Melanie Lee, Stuart Bradley, and Ninfa Fragale for animal husbandry. This work was supported by a Wellcome Trust International Prize Traveling Fellowship (63370) to M.A.B., NIH grants CA59998 and DK062345 and the Polycystic Kidney Disease Foundation (J.D.L.), NIH grant CA78711 (G.R.M.), and a Wellcome Trust grant (072111) (I.M. and M.A.B.). The Mount Sinai Mouse Genetics Facility was supported by NIH grant CA08830. The authors state that they have no competing interests.",

year = "2005",

month = feb,

doi = "10.1016/j.devcel.2004.12.004",

language = "English (US)",

volume = "8",

pages = "229--239",

journal = "Developmental cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "2",

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TY - JOUR

T1 - Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction

AU - Basson, M. Albert

AU - Akbulut, Simge

AU - Watson-Johnson, Judy

AU - Simon, Ruth

AU - Carroll, Thomas J.

AU - Shakya, Reena

AU - Gross, Isabelle

AU - Martin, Gail R.

AU - Lufkin, Thomas

AU - McMahon, Andrew P.

AU - Wilson, Patricia D.

AU - Costantini, Frank D.

AU - Mason, Ivor J.

AU - Licht, Jonathan D.

N1 - Funding Information: We thank Kevin Kelly for blastocyst injections, Uta Grieshammer for in situ probes and insightful comments on the manuscript, Debra Morrison for initial characterization of the Spry1 BAC clones, Vivette d’Agati, Adrian Woolf, Francesca Cole, Debbie Hyink, Imelda McGonnel, and Clemens Kiecker for helpful advice, and Melanie Lee, Stuart Bradley, and Ninfa Fragale for animal husbandry. This work was supported by a Wellcome Trust International Prize Traveling Fellowship (63370) to M.A.B., NIH grants CA59998 and DK062345 and the Polycystic Kidney Disease Foundation (J.D.L.), NIH grant CA78711 (G.R.M.), and a Wellcome Trust grant (072111) (I.M. and M.A.B.). The Mount Sinai Mouse Genetics Facility was supported by NIH grant CA08830. The authors state that they have no competing interests.

PY - 2005/2

Y1 - 2005/2

N2 - Intercellular signaling molecules and their receptors, whose expression must be tightly regulated in time and space, coordinate organogenesis. Regulators of intracellular signaling pathways provide an additional level of control. Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice. Spry1-/- embryos have supernumerary ureteric buds, resulting in the development of multiple ureters and multiplex kidneys. These defects are due to increased sensitivity of the Wolffian duct to GDNF/RET signaling, and reducing Gdnf gene dosage correspondingly rescues the Spry1 null phenotype. We conclude that the function of Spry1 is to modulate GDNF/RET signaling in the Wolffian duct, ensuring that kidney induction is restricted to a single site. These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations.

AB - Intercellular signaling molecules and their receptors, whose expression must be tightly regulated in time and space, coordinate organogenesis. Regulators of intracellular signaling pathways provide an additional level of control. Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice. Spry1-/- embryos have supernumerary ureteric buds, resulting in the development of multiple ureters and multiplex kidneys. These defects are due to increased sensitivity of the Wolffian duct to GDNF/RET signaling, and reducing Gdnf gene dosage correspondingly rescues the Spry1 null phenotype. We conclude that the function of Spry1 is to modulate GDNF/RET signaling in the Wolffian duct, ensuring that kidney induction is restricted to a single site. These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations.

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JO - Developmental cell

JF - Developmental cell

IS - 2

ER -

Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction

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