TY - JOUR
T1 - Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes
AU - Itman, Catherine Mary
AU - Small, Chris
AU - Griswold, Michael
AU - Nagaraja, Ankur K
AU - Matzuk, Martin M
AU - Brown, Chester W
AU - Jans, David Andrew
AU - Loveland, Katherine Ann Lakoski
PY - 2009
Y1 - 2009
N2 - 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. (c) 2009 Wiley-Liss, Inc.
AB - 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. (c) 2009 Wiley-Liss, Inc.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19517569
U2 - 10.1002/dvdy.21995
DO - 10.1002/dvdy.21995
M3 - Article
SN - 1058-8388
VL - 238
SP - 1688
EP - 1700
JO - Developmental Dynamics
JF - Developmental Dynamics
IS - 7
ER -