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Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes
Author(s) -
Itman Catherine,
Small Chris,
Griswold Michael,
Nagaraja Ankur K.,
Matzuk Martin M.,
Brown Chester W.,
Jans David A.,
Loveland Kate L.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21995
Subject(s) - sertoli cell , activin type 2 receptors , biology , smad , acvr2b , microbiology and biotechnology , medicine , endocrinology , tgf beta signaling pathway , signal transduction , smad2 protein , activin receptor , transforming growth factor , spermatogenesis
Activin is required for testis development. Activin signals via phosphorylation and nuclear accumulation of SMAD2 and SMAD3. We present novel findings of developmentally regulated activin signaling leading to specific transcriptional outcomes in testicular Sertoli cells. In immature, proliferating, Sertoli cells, activin A induces nuclear accumulation of SMAD3, but not SMAD2, although both proteins become phosphorylated. In postmitotic differentiating cells, both SMAD proteins accumulate in the nucleus. Furthermore, immature Sertoli cells are sensitive to activin dosage; higher concentrations induce maximal SMAD3 nuclear accumulation and a small increase in nuclear SMAD2. Microarray analysis identified distinct transcriptional outcomes correlating with differential SMAD utilization and new activin target genes, including Gja1 and Serpina5 , which are essential for Sertoli cell development and male fertility. In transgenic mice with altered activin bioactivity that display fertility phenotypes, Gja1 and Serpina5 are significantly altered. Thus, differential SMAD utilization in response to activin features during Sertoli cell maturation. Developmental Dynamics 238:1688–1700, 2009. © 2009 Wiley‐Liss, Inc.