Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia
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 o...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Ching, Saunders T. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014transfer abstract |
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| Schlagwörter: |
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| Umfang: |
11 |
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| Übergeordnetes Werk: |
Enthalten in: 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY - 2011, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:386 ; year:2014 ; number:1 ; day:1 ; month:02 ; pages:1-11 ; extent:11 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.ydbio.2013.12.014 |
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ELV028433971 |
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| 520 | |a 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. | ||
| 520 | |a 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. | ||
| 650 | 7 | |a FGF |2 Elsevier | |
| 650 | 7 | |a Urethra |2 Elsevier | |
| 650 | 7 | |a Hypospadias |2 Elsevier | |
| 650 | 7 | |a Genital tubercle |2 Elsevier | |
| 650 | 7 | |a Sprouty |2 Elsevier | |
| 700 | 1 | |a Cunha, Gerald R. |4 oth | |
| 700 | 1 | |a Baskin, Laurence S. |4 oth | |
| 700 | 1 | |a Basson, M. Albert |4 oth | |
| 700 | 1 | |a Klein, Ophir D. |4 oth | |
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10.1016/j.ydbio.2013.12.014 doi GBVA2014020000018.pica (DE-627)ELV028433971 (ELSEVIER)S0012-1606(13)00659-3 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Ching, Saunders T. verfasserin aut Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. FGF Elsevier Urethra Elsevier Hypospadias Elsevier Genital tubercle Elsevier Sprouty Elsevier Cunha, Gerald R. oth Baskin, Laurence S. oth Basson, M. Albert oth Klein, Ophir D. oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:386 year:2014 number:1 day:1 month:02 pages:1-11 extent:11 https://doi.org/10.1016/j.ydbio.2013.12.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 386 2014 1 1 0201 1-11 11 045F 570 |
| spelling |
10.1016/j.ydbio.2013.12.014 doi GBVA2014020000018.pica (DE-627)ELV028433971 (ELSEVIER)S0012-1606(13)00659-3 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Ching, Saunders T. verfasserin aut Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. FGF Elsevier Urethra Elsevier Hypospadias Elsevier Genital tubercle Elsevier Sprouty Elsevier Cunha, Gerald R. oth Baskin, Laurence S. oth Basson, M. Albert oth Klein, Ophir D. oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:386 year:2014 number:1 day:1 month:02 pages:1-11 extent:11 https://doi.org/10.1016/j.ydbio.2013.12.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 386 2014 1 1 0201 1-11 11 045F 570 |
| allfields_unstemmed |
10.1016/j.ydbio.2013.12.014 doi GBVA2014020000018.pica (DE-627)ELV028433971 (ELSEVIER)S0012-1606(13)00659-3 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Ching, Saunders T. verfasserin aut Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. FGF Elsevier Urethra Elsevier Hypospadias Elsevier Genital tubercle Elsevier Sprouty Elsevier Cunha, Gerald R. oth Baskin, Laurence S. oth Basson, M. Albert oth Klein, Ophir D. oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:386 year:2014 number:1 day:1 month:02 pages:1-11 extent:11 https://doi.org/10.1016/j.ydbio.2013.12.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 386 2014 1 1 0201 1-11 11 045F 570 |
| allfieldsGer |
10.1016/j.ydbio.2013.12.014 doi GBVA2014020000018.pica (DE-627)ELV028433971 (ELSEVIER)S0012-1606(13)00659-3 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Ching, Saunders T. verfasserin aut Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. FGF Elsevier Urethra Elsevier Hypospadias Elsevier Genital tubercle Elsevier Sprouty Elsevier Cunha, Gerald R. oth Baskin, Laurence S. oth Basson, M. Albert oth Klein, Ophir D. oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:386 year:2014 number:1 day:1 month:02 pages:1-11 extent:11 https://doi.org/10.1016/j.ydbio.2013.12.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 386 2014 1 1 0201 1-11 11 045F 570 |
| allfieldsSound |
10.1016/j.ydbio.2013.12.014 doi GBVA2014020000018.pica (DE-627)ELV028433971 (ELSEVIER)S0012-1606(13)00659-3 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 570 540 VZ Ching, Saunders T. verfasserin aut Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. FGF Elsevier Urethra Elsevier Hypospadias Elsevier Genital tubercle Elsevier Sprouty Elsevier Cunha, Gerald R. oth Baskin, Laurence S. oth Basson, M. Albert oth Klein, Ophir D. oth Enthalten in Elsevier 326 oral DOSE RESPONSE OF NORMAL LUNG DURING RT ASSESSED BY CONE BEAM CT – A POTENTIAL TOOL FOR BIOLOGICALLY ADAPTIVE RADIATION THERAPY 2011 Amsterdam [u.a.] (DE-627)ELV010652000 volume:386 year:2014 number:1 day:1 month:02 pages:1-11 extent:11 https://doi.org/10.1016/j.ydbio.2013.12.014 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_147 GBV_ILN_2018 GBV_ILN_2034 AR 386 2014 1 1 0201 1-11 11 045F 570 |
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Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia |
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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. |
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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. |
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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. |
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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. 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