Role of fibroblast growth factor receptor 2 in kidney mesenchyme

David Hains, Sunder Sims-Lucas, Kayle Kish, Monalee Saha, Kirk Mchugh, Carlton M. Bates

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Conditional deletion of murine fibroblast growth factor receptors (Fgfrs) 1 and 2 in metanephric mesenchyme leads to renal agenesis with unbranched ureteric buds; however, there are occasionally two buds per nephric duct. Our goal was to determine whether conditional deletion of Fgfr1 or Fgfr2 alone resulted in multiple ureteric bud induction sites. Although deletion of Fgfr1 alone results in no abnormalities, loss of Fgfr2 often leads to multiple ureteric buds and anomalies including renal aplasia, misshaped kidneys, partially duplicated kidneys, duplicated ureters, and obstructed hydroureter. Deletion of Fgfr2 did not change expression domains of glial cell line-derived neurotrophic factor (GDNF), Robo2, bone morphogenetic protein 4, or Sprouty1, all of which regulate ureteric bud induction. Cultured Fgfr2 mutant nephric ducts were also not more sensitive to exogenous GDNF than controls. Whole mount in situ hybridization revealed that in mutant embryos, Fgfr2 was deleted from stromal cells around the nephric duct and ureteric bud base, which correlates well with the ureteric bud induction abnormalities. Thus, Fgfr2 is critical in ensuring that there is a single ureteric bud from the nephric duct. The plethora of later stage defects in Fgfr2 conditional knockouts is reminiscent of many human cases of genetic urogenital anomalies.

Original languageEnglish (US)
Pages (from-to)592-598
Number of pages7
JournalPediatric Research
Volume64
Issue number6
DOIs
StatePublished - Dec 1 2008

Fingerprint

Receptor, Fibroblast Growth Factor, Type 2
Mesoderm
Kidney
Glial Cell Line-Derived Neurotrophic Factor
Receptor, Fibroblast Growth Factor, Type 1
Bone Morphogenetic Protein 4
Medical Genetics
Ureter
Stromal Cells
In Situ Hybridization
Embryonic Structures

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Hains, D., Sims-Lucas, S., Kish, K., Saha, M., Mchugh, K., & Bates, C. M. (2008). Role of fibroblast growth factor receptor 2 in kidney mesenchyme. Pediatric Research, 64(6), 592-598. https://doi.org/10.1203/PDR.0b013e318187cc12

Role of fibroblast growth factor receptor 2 in kidney mesenchyme. / Hains, David; Sims-Lucas, Sunder; Kish, Kayle; Saha, Monalee; Mchugh, Kirk; Bates, Carlton M.

In: Pediatric Research, Vol. 64, No. 6, 01.12.2008, p. 592-598.

Research output: Contribution to journalArticle

Hains, D, Sims-Lucas, S, Kish, K, Saha, M, Mchugh, K & Bates, CM 2008, 'Role of fibroblast growth factor receptor 2 in kidney mesenchyme', Pediatric Research, vol. 64, no. 6, pp. 592-598. https://doi.org/10.1203/PDR.0b013e318187cc12
Hains, David ; Sims-Lucas, Sunder ; Kish, Kayle ; Saha, Monalee ; Mchugh, Kirk ; Bates, Carlton M. / Role of fibroblast growth factor receptor 2 in kidney mesenchyme. In: Pediatric Research. 2008 ; Vol. 64, No. 6. pp. 592-598.
@article{13f8f2edb83f4c16b13af1d82fbd9b3a,
title = "Role of fibroblast growth factor receptor 2 in kidney mesenchyme",
abstract = "Conditional deletion of murine fibroblast growth factor receptors (Fgfrs) 1 and 2 in metanephric mesenchyme leads to renal agenesis with unbranched ureteric buds; however, there are occasionally two buds per nephric duct. Our goal was to determine whether conditional deletion of Fgfr1 or Fgfr2 alone resulted in multiple ureteric bud induction sites. Although deletion of Fgfr1 alone results in no abnormalities, loss of Fgfr2 often leads to multiple ureteric buds and anomalies including renal aplasia, misshaped kidneys, partially duplicated kidneys, duplicated ureters, and obstructed hydroureter. Deletion of Fgfr2 did not change expression domains of glial cell line-derived neurotrophic factor (GDNF), Robo2, bone morphogenetic protein 4, or Sprouty1, all of which regulate ureteric bud induction. Cultured Fgfr2 mutant nephric ducts were also not more sensitive to exogenous GDNF than controls. Whole mount in situ hybridization revealed that in mutant embryos, Fgfr2 was deleted from stromal cells around the nephric duct and ureteric bud base, which correlates well with the ureteric bud induction abnormalities. Thus, Fgfr2 is critical in ensuring that there is a single ureteric bud from the nephric duct. The plethora of later stage defects in Fgfr2 conditional knockouts is reminiscent of many human cases of genetic urogenital anomalies.",
author = "David Hains and Sunder Sims-Lucas and Kayle Kish and Monalee Saha and Kirk Mchugh and Bates, {Carlton M.}",
year = "2008",
month = "12",
day = "1",
doi = "10.1203/PDR.0b013e318187cc12",
language = "English (US)",
volume = "64",
pages = "592--598",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Role of fibroblast growth factor receptor 2 in kidney mesenchyme

AU - Hains, David

AU - Sims-Lucas, Sunder

AU - Kish, Kayle

AU - Saha, Monalee

AU - Mchugh, Kirk

AU - Bates, Carlton M.

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Conditional deletion of murine fibroblast growth factor receptors (Fgfrs) 1 and 2 in metanephric mesenchyme leads to renal agenesis with unbranched ureteric buds; however, there are occasionally two buds per nephric duct. Our goal was to determine whether conditional deletion of Fgfr1 or Fgfr2 alone resulted in multiple ureteric bud induction sites. Although deletion of Fgfr1 alone results in no abnormalities, loss of Fgfr2 often leads to multiple ureteric buds and anomalies including renal aplasia, misshaped kidneys, partially duplicated kidneys, duplicated ureters, and obstructed hydroureter. Deletion of Fgfr2 did not change expression domains of glial cell line-derived neurotrophic factor (GDNF), Robo2, bone morphogenetic protein 4, or Sprouty1, all of which regulate ureteric bud induction. Cultured Fgfr2 mutant nephric ducts were also not more sensitive to exogenous GDNF than controls. Whole mount in situ hybridization revealed that in mutant embryos, Fgfr2 was deleted from stromal cells around the nephric duct and ureteric bud base, which correlates well with the ureteric bud induction abnormalities. Thus, Fgfr2 is critical in ensuring that there is a single ureteric bud from the nephric duct. The plethora of later stage defects in Fgfr2 conditional knockouts is reminiscent of many human cases of genetic urogenital anomalies.

AB - Conditional deletion of murine fibroblast growth factor receptors (Fgfrs) 1 and 2 in metanephric mesenchyme leads to renal agenesis with unbranched ureteric buds; however, there are occasionally two buds per nephric duct. Our goal was to determine whether conditional deletion of Fgfr1 or Fgfr2 alone resulted in multiple ureteric bud induction sites. Although deletion of Fgfr1 alone results in no abnormalities, loss of Fgfr2 often leads to multiple ureteric buds and anomalies including renal aplasia, misshaped kidneys, partially duplicated kidneys, duplicated ureters, and obstructed hydroureter. Deletion of Fgfr2 did not change expression domains of glial cell line-derived neurotrophic factor (GDNF), Robo2, bone morphogenetic protein 4, or Sprouty1, all of which regulate ureteric bud induction. Cultured Fgfr2 mutant nephric ducts were also not more sensitive to exogenous GDNF than controls. Whole mount in situ hybridization revealed that in mutant embryos, Fgfr2 was deleted from stromal cells around the nephric duct and ureteric bud base, which correlates well with the ureteric bud induction abnormalities. Thus, Fgfr2 is critical in ensuring that there is a single ureteric bud from the nephric duct. The plethora of later stage defects in Fgfr2 conditional knockouts is reminiscent of many human cases of genetic urogenital anomalies.

UR - http://www.scopus.com/inward/record.url?scp=57849115762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57849115762&partnerID=8YFLogxK

U2 - 10.1203/PDR.0b013e318187cc12

DO - 10.1203/PDR.0b013e318187cc12

M3 - Article

VL - 64

SP - 592

EP - 598

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 6

ER -