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Importance of forkhead transcription factor Fkhl18 for development of testicular vasculature
Author(s) -
Sato Yuko,
Baba Takashi,
Zubair Mohamad,
Miyabayashi Kanako,
Toyama Yoshiro,
Maekawa Mamiko,
Owaki Akiko,
Mizusaki Hirofumi,
Sawamura Tatsuya,
Toshimori Kiyotaka,
Morohashi KenIchirou,
KatohFukui Yuko
Publication year - 2008
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.20888
Subject(s) - biology , transcription factor , apoptosis , subfamily , ectopic expression , gene , fetus , microbiology and biotechnology , endocrinology , genetics , pregnancy
Abstract Forkhead transcription factors are characterized by a winged helix DNA binding domain, and the members of this family are classified into 20 subclasses by phylogenetic analyses. Fkhl18 is structurally unique, and is classified into FoxS subfamily. We found Fkhl18 expression in periendothelial cells of the developing mouse fetal testis. In an attempt to clarify its function, we generated mice with Fkhl18 gene disruption. Although KO mice developed normally and were fertile in both sexes, we frequently noticed unusual blood accumulation in the fetal testis. Electron microscopic analysis demonstrated frequent gaps, measuring 100–400 nm, in endothelial cells of blood vessels. These gaps probably represented ectopic apoptosis of testicular periendothelial cells, identified by caspase‐3 expression, in KO fetuses. No apoptosis of endothelial cells was noted. Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4. Considering that Fas ligand gene expression is activated by Foxs, the elevated activity of Foxs in the absence of Fkhl18 probably explains the marked apoptosis of periendothelial cells in Fkhl18 KO mice. Mol. Reprod. Dev. 75: 1361–1371, 2008. © 2008 Wiley‐Liss, Inc.