Serum response factor, its cofactors, and epithelial-mesenchymal signaling in urinary bladder smooth muscle formation.
Little is known about the mechanism of bladder smooth muscle differentiation. We hypothesize that epithelial-mesenchymal signaling induces the expression of smooth muscle proteins in bladder mesenchyme resulting in smooth muscle differentiation. We confirmed that smooth muscle differentiation in the mouse urinary bladder occurs first at gestational day 14 (E14) based upon immunohistochemical localization of smooth muscle alpha-actin (SMAA). To investigate murine bladder smooth muscle differentiation and epithlelial-mesenchymal signaling in the developing bladder, we analyzed gene expression profiles of intact embryonic murine bladders and separated epithelial and mesenchymal components at embryonic days E13, E14, E15, E16, and postnatal day 1 (P1). Using cDNA microarray, we identified regulators of vascular smooth muscle differentiation in bladder mesenchyme, including serum response factor (SRF) and its cofactors, ELK1 and SRF accessory protein (SAP)1, as well as two SRF-associated pathways, angiotension receptor II and transforming growth factor- beta2. Immunohistochemistry showed diffuse expression of SRF in the bladder at E12 with localization of expression to the peripheral mesenchyme at E13 and E14. Our results suggest that bladder smooth muscle differentiation may share a similar gene expression program as occurs during vascular smooth muscle differentiation. The unique structure of the urinary bladder makes it an ideal model for studies of smooth muscle differentiation and epithelial-mesenchymal signaling.
Li
Jiang
J
Department of Urology University of California 400 Parnassus Avenue, ACC-610 California 94143-0738 San Francisco, USA.
Shiroyanagi
Yoshiyuki
Y
Lin
Guiting
G
Haqq
Christopher
C
Lin
Ching-Shwun
CS
Lue
Tom F
TF
Willingham
Emily
E
Baskin
Laurence S
LS
D000818:Animals; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011945:Receptors, Angiotensin / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053781:Transforming Growth Factor beta2; D001743:Urinary Bladder / Q000196:embryology*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D050808:ets-Domain Protein Elk-4 / Q000378:metabolism
C494113:Elk1 protein, mouse; D011945:Receptors, Angiotensin; D026362:Serum Response Factor; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4