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Endoderm Formation and Patterning in the Mouse

小鼠内胚层的形成和图案化

基本信息

批准号：
7269445
负责人：
ELIZABETH J ROBERTSON
金额：
$ 23.04万
依托单位：
UNIVERSITY OF OXFORD
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-01-14 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7269445
关键词：
Activins Alleles Alternative Splicing Amino Acids Anterior Cell Fate Control Cell Lineage Development Development Plans ES Cell Line Embryo Endoderm Endoderm Cell Gastrocoele Gastrointestinal tract structure Gene Targeting Germ Layers Heart Knock-in Mouse Knowledge Liver Lung Mediator of activation protein Molecular Mouse Strains Mus Mutagenesis Mutant Strains Mice Mutation Nodal Pancreas Pathway interactions Pattern Pattern Formation Play Protein Isoforms Rana Regulatory Element Role Signal Transduction Staging Testing Thymus Gland Thyroid Gland Tissues Transcript Transcription Coactivator Transcription Repressor/Corepressor Transgenic Organisms Tube Undifferentiated Xenopus Zinc Fingers embryonic stem cell gain of function genetic manipulation in vivo loss of function mutation novel recombinase research study selective expression

项目摘要

The definitive endoderm, one of the three primary germ layers of the early embryo gives rise to the 3rimitive gut tube, which in turn contributes to a diverse set of tissues including the thyroid, thymus, liver, lungs and digestive tract. Signals from the definitive endoderm also play essential roles during the induction and patterning of the heart and anterior CNS. We recently identified Smad2, an effector downstream of TGFb/activin/nodal signals as an essential regulator of endoderm formation in the mouse. To dissect potentially unique and/or overlapping Smad2/3 activities, Smad2 deficient ES cells transfected with expression constructs will be tested for their ability to colonize the definitive endoderm lineage. Functional activities of novel "knock-in" alleles expressing different Smad2/3 isoforms under control of endogenous Smad2 regulatory elements will also be tested. To evaluate the roles of TGFb signaling during patterning and formation of endodermal derivatives, we will exploit conditional alleles of Smad2 and Smad4 in combination with transgenic mouse strains expressing Cre in different temporal and spatial domains of the gut lineage, including the developing liver and pancreas. The zinc finger transcriptional repressor Blimp1 has been shown to control endodermal versus mesodermal fates in the frog embryo. We will generate and analyze a loss of function mutation at the mouse Blimp1 locus to test for possibly conserved function in endoderm formation. Finally to identify target genes required for endoderm formation we perform transcriptional profiling using Smad2, Smad4, Foxhl, and Mix-1 deficient ES cells induced to differentiate into endoderm in culture. Experiments outlined in this proposal aim to enhance our knowledge of how Smad2 and other transcriptional mediators control cell fate, proliferation and differentiation of the endodermal cell lineage.

最终的内胚层，早期胚胎的三个主要胚层之一，产生胚层