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Kruppel-like factor 5 is required for formation and differentiation of the bladder urothelium

Kruppel-like factor 5 is required for formation and differentiation of the bladder urothelium
Kruppel-like factor 5 is required for formation and differentiation of the bladder urothelium
Kruppel-like transcription factor 5 (Klf5) was detected in the developing and mature murine bladder urothelium. Herein we report a critical role of KLF5 in the formation and terminal differentiation of the urothelium. The Shh(GfpCre) transgene was used to delete the Klf5(floxed) alleles from bladder epithelial cells causing prenatal hydronephrosis, hydroureter, and vesicoureteric reflux. The bladder urothelium failed to stratify and did not express terminal differentiation markers characteristic of basal, intermediate, and umbrella cells including keratins 20, 14, and 5, and the uroplakins. The effects of Klf5 deletion were unique to the developing bladder epithelium since maturation of the epithelium comprising the bladder neck and urethra was unaffected by the lack of KLF5. mRNA analysis identified reductions in Ppar?, Grhl3, Elf3, and Ovol1expression in Klf5 deficient fetal bladders supporting their participation in a transcriptional network regulating bladder urothelial differentiation. KLF5 regulated expression of the mGrhl3 promoter in transient transfection assays. The absence of urothelial Klf5 altered epithelial-mesenchymal signaling leading to the formation of an ectopic alpha smooth muscle actin positive layer of cells subjacent to the epithelium and a thinner detrusor muscle that was not attributable to disruption of SHH signaling, a known mediator of detrusor morphogenesis. Deletion of Klf5 from the developing bladder urothelium blocked epithelial cell differentiation, impaired bladder morphogenesis and function causing hydroureter and hydronephrosis at birth.
0012-1606
79-90
Bell, Sheila M.
49b8f50b-b545-4579-9483-c1db6e26b127
Zhang, Liqian
9ffbb2ce-b251-4c3c-8c06-1cb798139728
Mendell, Angela
9d1b5b59-0830-4343-995e-c734e8a1d7ae
Xu, Yan
2b4952f1-3855-4a5d-a8b0-777561a292e1
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Lessard, James L.
3bdd0ca7-1ea6-43aa-8c6d-8227042e8029
Whitsett, Jeffrey A.
84fb8fc3-212e-4741-8934-d4083cd6549b
Bell, Sheila M.
49b8f50b-b545-4579-9483-c1db6e26b127
Zhang, Liqian
9ffbb2ce-b251-4c3c-8c06-1cb798139728
Mendell, Angela
9d1b5b59-0830-4343-995e-c734e8a1d7ae
Xu, Yan
2b4952f1-3855-4a5d-a8b0-777561a292e1
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Lessard, James L.
3bdd0ca7-1ea6-43aa-8c6d-8227042e8029
Whitsett, Jeffrey A.
84fb8fc3-212e-4741-8934-d4083cd6549b

Bell, Sheila M., Zhang, Liqian, Mendell, Angela, Xu, Yan, Haitchi, Hans Michael, Lessard, James L. and Whitsett, Jeffrey A. (2011) Kruppel-like factor 5 is required for formation and differentiation of the bladder urothelium. Developmental Biology, 358 (1), 79-90. (doi:10.1016/j.ydbio.2011.07.020). (PMID:21803035)

Record type: Article

Abstract

Kruppel-like transcription factor 5 (Klf5) was detected in the developing and mature murine bladder urothelium. Herein we report a critical role of KLF5 in the formation and terminal differentiation of the urothelium. The Shh(GfpCre) transgene was used to delete the Klf5(floxed) alleles from bladder epithelial cells causing prenatal hydronephrosis, hydroureter, and vesicoureteric reflux. The bladder urothelium failed to stratify and did not express terminal differentiation markers characteristic of basal, intermediate, and umbrella cells including keratins 20, 14, and 5, and the uroplakins. The effects of Klf5 deletion were unique to the developing bladder epithelium since maturation of the epithelium comprising the bladder neck and urethra was unaffected by the lack of KLF5. mRNA analysis identified reductions in Ppar?, Grhl3, Elf3, and Ovol1expression in Klf5 deficient fetal bladders supporting their participation in a transcriptional network regulating bladder urothelial differentiation. KLF5 regulated expression of the mGrhl3 promoter in transient transfection assays. The absence of urothelial Klf5 altered epithelial-mesenchymal signaling leading to the formation of an ectopic alpha smooth muscle actin positive layer of cells subjacent to the epithelium and a thinner detrusor muscle that was not attributable to disruption of SHH signaling, a known mediator of detrusor morphogenesis. Deletion of Klf5 from the developing bladder urothelium blocked epithelial cell differentiation, impaired bladder morphogenesis and function causing hydroureter and hydronephrosis at birth.

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More information

Accepted/In Press date: 9 July 2011
e-pub ahead of print date: 22 July 2011
Published date: 1 October 2011
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 386156
URI: http://eprints.soton.ac.uk/id/eprint/386156
ISSN: 0012-1606
PURE UUID: 9efe850e-3a87-4e6a-b55b-bb5df5e717af
ORCID for Hans Michael Haitchi: ORCID iD orcid.org/0000-0001-8603-302X

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Date deposited: 28 Jan 2016 15:16
Last modified: 15 Mar 2024 03:14

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Contributors

Author: Sheila M. Bell
Author: Liqian Zhang
Author: Angela Mendell
Author: Yan Xu
Author: James L. Lessard
Author: Jeffrey A. Whitsett

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