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Gene regulatory networks controlling functional activities of spatially and temporally distinct endodermal cell populations in the early mouse embryo remain ill defined. The T-box transcription factor Eomes, acting downstream from Nodal/Smad signals, directly activates the LIM domain homeobox transcription factor Lhx1 in the visceral endoderm. Here we demonstrate Smad4/Eomes-dependent Lhx1 expression in the epiblast marks the entire definitive endoderm lineage, the anterior mesendoderm, and midline progenitors. Conditional inactivation of Lhx1 disrupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. Moreover, in proteomic experiments, we characterized a complex comprised of Lhx1, Otx2, and Foxa2 as well as the chromatin-looping protein Ldb1. These partnerships cooperatively regulate development of the anterior mesendoderm, node, and midline cell populations responsible for establishment of the left-right body axis and head formation.
This article was published in the following journal.
Name: Genes & development
The LIM-homeodomain (LIM-HD) transcription factor Islet-1 (Isl1) interacts with the LIM domain binding protein 1 (Ldb1) co-regulator to control expression of key pancreatic β-cell genes. However, Ldb...
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Preterm children have a high risk for neurodevelopmental impairments. The impact on motor functions and neurosensory functions is demonstrated but the incidenceof executive functions is no...
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The physiological mechanisms that govern the rhythmic occurrence of certain biochemical, physiological, and behavioral phenomena in plants and animals.
Customary standards that govern behavior in groups, cultures, or societies. They reflect what a group deems acceptable in a social context in terms of appropriate and inappropriate values, beliefs, attitudes, and behaviors.
Containers, packaging, and packaging materials for drugs and biological products. These include those in ampule, capsule, tablet, solution or other forms. Packaging includes immediate-containers, secondary-containers, and cartons. In the United States, such packaging is controlled under the Federal Food, Drug, and Cosmetic Act which also stipulates requirements for tamper-resistance and child-resistance. Similar laws govern use elsewhere. (From Code of Federal Regulations, 21 CFR 1 Section 210, 1993) DRUG LABELING is also available.
A toxic thiol mercury salt formerly used as a diuretic. It inhibits various biochemical functions, especially in mitochondria, and is used to study those functions.
Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...