(The) effect of serum response factor (SRF) on the FAST-1-dependent activin signaling혈청반응인자(SRF)가 FAST-1 의존적인 Activin 신호전달에 미치는 영향 연구

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Activin is a member of TGF-beta superfamily of growth and differentiation factors and has been shown to play a role in regulation of reproductive endocrine system, erythroid differentiation and mesoderm-induction of an embryo. Serum response factor (SRF) is a MADS box-containing transcription factor mediating the rapid transcriptional response to extracellular stimuli such as growth, stress, or differentiation signals. In this study, it was found that SRF inhibited Activin/FAST-1-dependent transcription using ARE-Luc reporter. SRF associated with both Smad2 and FAST-1 mediating Activin/FAST-1-dependent transcription. Furthermore, MH2 domain of Smad2 was required for interaction of Smad2 with SRF. MADS box domain of SRF interacted with FAST-1 and suppressed Activin/FAST-1-dependent transcription. It was also found that SRF associated with forkhead DNA-binding domain of FAST-1. SRF did not suppress either phosphorylation of Smad2 or Smad2-Smad4 complex formation induced by Activin. However, SRF reduced Activin-induced formation of Smad2-FAST-1 complex. Because Activin/FAST-1-dependent transcription is essential for the mesoderm induction and axial patterning in Xenopus embryos, functions of Xenopus SRF (XSRF) in Xenopus early embryos were also examined. Ectopic expression of XSRF RNA inhibited mesoderm induction, both in marginal zone in vivo and by Activin signal in animal caps, and it also caused the embryonic malformations shown at later stages including anterior truncation and shortened body axis. These phenotypic defects were rescued by coexpression of a constitutively active form of FAST-1. Conversely, morpholino-mediated depletion of XSRF expanded the expression of mesodermal genes toward the ectodermal territory, and caused not only the severely shortened body axis and truncation of anterior structures but also defective gastrulation movement in Xenopus embryos. These axial defects by XSRF morpholino were rescued by coexpression of a constitutively repre...
Koh, Gou-YoungresearcherChung, An-Sikresearcher고규영researcher정안식researcher
한국과학기술원 : 생명과학과,
Issue Date
263439/325007  / 020005206

학위논문(박사) - 한국과학기술원 : 생명과학과, 2007.2, [ x, 92 p. ]


FAST-1; Xenopus; Gastrulation; Activin; 혈청반응인자; FAST-1; 개구리; 낭배형성; Activin; SRF

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