Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes

Catherine Itman; C Small; M Griswold; A K Nagaraja; M M Matzuk; C W Brown; D A Jans; K L Loveland

doi:10.1002/dvdy.21995

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Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes

Journal article

Peer reviewed

Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes

Catherine Itman, C Small, M Griswold, A K Nagaraja, M M Matzuk, C W Brown, D A Jans and K L Loveland

Developmental Dynamics, Vol.238(7), pp.1688-1700

2009

DOI: https://doi.org/10.1002/dvdy.21995

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Abstract

morphogen gradient

development

TGFβ

Sertoli

testis

Rarres1

TIG-1

PDGF

Gja1

Serpina5

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. © 2009 Wiley-Liss, Inc.

Details

Title: Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes
Authors: Catherine Itman (Author) - Monash University
C Small (Author) - Washington State University, United States
M Griswold (Author) - Washington State University, United States
A K Nagaraja (Author) - Baylor College of Medicine, Texas
M M Matzuk (Author) - Baylor College of Medicine, Texas
C W Brown (Author) - Baylor College of Medicine, Texas
D A Jans (Author) - Monash University
K L Loveland (Author) - Monash University
Publication details: Developmental Dynamics, Vol.238(7), pp.1688-1700
Publisher: John Wiley & Sons Inc.
Date published: 2009
DOI: 10.1002/dvdy.21995
ISSN: 1058-8388
Organisation Unit: University of the Sunshine Coast, Queensland
Language: English
Record Identifier: 99450194702621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Anatomy & Morphology; Developmental Biology

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