Genome-wide expression profiling of urinary bladder implicates desmosomai and cytoskeletal dysregulation in the bladder exstrophy-epispadias complex

Lihong Qi, Kun Chen, David J. Hur, Garima Yagnik, Yegappan Lakshmanan, Lori E. Kotch, Gerald H. Ashrafi, Francisco Martinez-Murillo, Jeanne Kowalski, Cyrill Naydenov, Lars Wittler, John P. Gearhart, Markus Draaken, Heiko Reutter, Michael Ludwig, Simeon Boyd

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The bladder exstrophy-epispadias complex (BEEC) represents a spectrum of urological abnormalities where part, or all, of the distal urinary tract fails to close during development, becoming exposed on the outer abdominal wall. While the etiology of BEEC remains unknown, strong evidence exists that genetic factors are implicated. To understand the pathways regulating embryonic bladder development and to identify high-probability BEEC candidate genes, we conducted a genome-wide expression profiling (GWEP) study using normal and exstrophic human urinary bladders and human and mouse embryologic bladder-precursor tissues. We identified 162 genes differentially expressed in both embryonic and postnatal human samples. Pathway analysis of these genes revealed 11 biological networks with top functions related to skeletal and muscular system development, cellular assembly and development, organ morphology, or connective tissue disorders. The two most down-regulated genes desmin (DES, fold-change, -74.7) and desmuslin (DMN, fold-change, -53.0) are involved in desmosome mediated cell-cell adhesion and cytoskeletal architecture. Intriguingly, the sixth most overexpressed gene was desmoplakin (DSP, fold-change, +48.8), the most abundant desmosomal protein. We found 30% of the candidate genes to be directly associated with desmosome structure/function or cytoskeletal assembly, pointing to desmosomal and/or cytoskeletal deregulation as an etiologic factor for BEEC. Further findings indicate that p63, PERP, SYNPO2 and the Wnt pathway may also contribute to BEEC etiology. This study provides the first expression profile of urogenital genes during bladder development and points to the high-probability candidate genes for BEEC.

Original languageEnglish (US)
Pages (from-to)755-765
Number of pages11
JournalInternational Journal of Molecular Medicine
Volume27
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Urinary Bladder
Genome
Genes
Desmosomes
Desmoplakins
Wnt Signaling Pathway
Desmin
Muscle Development
Abdominal Wall
Bladder Exstrophy and Epispadias Complex
Urinary Tract
Transcriptome
Cell Adhesion
Connective Tissue
Embryonic Development
Proteins

Keywords

  • Bladder development
  • Bladder exstrophy
  • Cytoskeletal assembly
  • Desmosomal assembly
  • Epispadias
  • Genome-wide expression profiling

ASJC Scopus subject areas

  • Genetics

Cite this

Genome-wide expression profiling of urinary bladder implicates desmosomai and cytoskeletal dysregulation in the bladder exstrophy-epispadias complex. / Qi, Lihong; Chen, Kun; Hur, David J.; Yagnik, Garima; Lakshmanan, Yegappan; Kotch, Lori E.; Ashrafi, Gerald H.; Martinez-Murillo, Francisco; Kowalski, Jeanne; Naydenov, Cyrill; Wittler, Lars; Gearhart, John P.; Draaken, Markus; Reutter, Heiko; Ludwig, Michael; Boyd, Simeon.

In: International Journal of Molecular Medicine, Vol. 27, No. 6, 06.2011, p. 755-765.

Research output: Contribution to journalArticle

Qi, L, Chen, K, Hur, DJ, Yagnik, G, Lakshmanan, Y, Kotch, LE, Ashrafi, GH, Martinez-Murillo, F, Kowalski, J, Naydenov, C, Wittler, L, Gearhart, JP, Draaken, M, Reutter, H, Ludwig, M & Boyd, S 2011, 'Genome-wide expression profiling of urinary bladder implicates desmosomai and cytoskeletal dysregulation in the bladder exstrophy-epispadias complex', International Journal of Molecular Medicine, vol. 27, no. 6, pp. 755-765. https://doi.org/10.3892/ijmm.2011.654
Qi, Lihong ; Chen, Kun ; Hur, David J. ; Yagnik, Garima ; Lakshmanan, Yegappan ; Kotch, Lori E. ; Ashrafi, Gerald H. ; Martinez-Murillo, Francisco ; Kowalski, Jeanne ; Naydenov, Cyrill ; Wittler, Lars ; Gearhart, John P. ; Draaken, Markus ; Reutter, Heiko ; Ludwig, Michael ; Boyd, Simeon. / Genome-wide expression profiling of urinary bladder implicates desmosomai and cytoskeletal dysregulation in the bladder exstrophy-epispadias complex. In: International Journal of Molecular Medicine. 2011 ; Vol. 27, No. 6. pp. 755-765.
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abstract = "The bladder exstrophy-epispadias complex (BEEC) represents a spectrum of urological abnormalities where part, or all, of the distal urinary tract fails to close during development, becoming exposed on the outer abdominal wall. While the etiology of BEEC remains unknown, strong evidence exists that genetic factors are implicated. To understand the pathways regulating embryonic bladder development and to identify high-probability BEEC candidate genes, we conducted a genome-wide expression profiling (GWEP) study using normal and exstrophic human urinary bladders and human and mouse embryologic bladder-precursor tissues. We identified 162 genes differentially expressed in both embryonic and postnatal human samples. Pathway analysis of these genes revealed 11 biological networks with top functions related to skeletal and muscular system development, cellular assembly and development, organ morphology, or connective tissue disorders. The two most down-regulated genes desmin (DES, fold-change, -74.7) and desmuslin (DMN, fold-change, -53.0) are involved in desmosome mediated cell-cell adhesion and cytoskeletal architecture. Intriguingly, the sixth most overexpressed gene was desmoplakin (DSP, fold-change, +48.8), the most abundant desmosomal protein. We found 30{\%} of the candidate genes to be directly associated with desmosome structure/function or cytoskeletal assembly, pointing to desmosomal and/or cytoskeletal deregulation as an etiologic factor for BEEC. Further findings indicate that p63, PERP, SYNPO2 and the Wnt pathway may also contribute to BEEC etiology. This study provides the first expression profile of urogenital genes during bladder development and points to the high-probability candidate genes for BEEC.",
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AU - Ashrafi, Gerald H.

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