Document Detail

Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.
MedLine Citation:
PMID:  22492356     Owner:  NLM     Status:  MEDLINE    
How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann-Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer.
Norihiro Sudou; Shinji Yamamoto; Hajime Ogino; Masanori Taira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  139     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-11     Completed Date:  2012-05-31     Revised Date:  2014-08-11    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  1651-61     Citation Subset:  IM    
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MeSH Terms
Chromatin Immunoprecipitation
Gene Expression Regulation, Developmental / genetics,  physiology*
Goosecoid Protein / metabolism*
Homeodomain Proteins / metabolism
In Situ Hybridization
Intercellular Signaling Peptides and Proteins / metabolism*
LIM-Homeodomain Proteins / metabolism
Models, Biological
Organizers, Embryonic / embryology*
Otx Transcription Factors / metabolism
Polymerase Chain Reaction
Regulatory Elements, Transcriptional / physiology*
T-Box Domain Proteins / metabolism
Transcription Factors / metabolism*
Xenopus / embryology*
Xenopus Proteins / metabolism*
Grant Support
P40 OD010997/OD/NIH HHS
Reg. No./Substance:
0/Goosecoid Protein; 0/Homeodomain Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/LIM-Homeodomain Proteins; 0/Lhx1 protein, Xenopus; 0/Mix.1 protein, Xenopus; 0/Otx Transcription Factors; 0/Otx2 protein, Xenopus; 0/T-Box Domain Proteins; 0/Transcription Factors; 0/VegT protein, Xenopus; 0/Xenopus Proteins; 0/cerberus protein, Xenopus

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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