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Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia.
- Source :
-
Developmental biology [Dev Biol] 2014 Feb 01; Vol. 386 (1), pp. 1-11. Date of Electronic Publication: 2013 Dec 18. - Publication Year :
- 2014
-
Abstract
- Development of the mammalian external genitalia is controlled by a network of signaling molecules and transcription factors. Because FGF signaling plays a central role in this complicated morphogenetic process, we investigated the role of Sprouty genes, which are important intracellular modulators of FGF signaling, during embryonic development of the external genitalia in mice. We found that Sprouty genes are expressed by the urethral epithelium during embryogenesis, and that they have a critical function during urethral canalization and fusion. Development of the genital tubercle (GT), the anlage of the prepuce and glans penis in males and glans clitoris in females, was severely affected in male embryos carrying null alleles of both Spry1 and Spry2. In Spry1(-/-);Spry2(-/-) embryos, the internal tubular urethra was absent, and urothelial morphology and organization was abnormal. These effects were due, in part, to elevated levels of epithelial cell proliferation in Spry1(-/-);Spry2(-/-) embryos. Despite changes in overall organization, terminal differentiation of the urothelium was not significantly affected. Characterization of the molecular pathways that regulate normal GT development confirmed that deletion of Sprouty genes leads to elevated FGF signaling, whereas levels of signaling in other cascades were largely preserved. Together, these results show that levels of FGF signaling must be tightly regulated during embryonic development of the external genitalia in mice, and that this regulation is mediated in part through the activity of Sprouty gene products.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Proliferation
Female
Fibroblast Growth Factors metabolism
Gene Deletion
Immunohistochemistry
In Situ Hybridization
MAP Kinase Signaling System
Male
Mice
Mice, Transgenic
Mutation
Protein Serine-Threonine Kinases
Signal Transduction
Time Factors
Urothelium embryology
Urothelium metabolism
Adaptor Proteins, Signal Transducing physiology
Gene Expression Regulation, Developmental
Genitalia embryology
Intracellular Signaling Peptides and Proteins physiology
Membrane Proteins physiology
Phosphoproteins physiology
Urethra embryology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-564X
- Volume :
- 386
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 24361260
- Full Text :
- https://doi.org/10.1016/j.ydbio.2013.12.014