Downstream targets of Isl1 in the hindlimb field and genital tubercle
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA835341 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Despite the incredible morphological diversity found within vertebrates, embryonic development is often regulated by shared foundational mechanism maintained from a common ancestor. For instance, the tetrapod limb displays tremendous variation in size and shape but largely develops according to conserved gene regulatory networks, including signaling pathways, transcription factors, and enhancers. The phallus of amniotes is also thought to share a basic homology originating from their last common ancestor over 300 million years ago. The genital tubercle (GT) of mammals – the embryonic precursor to the penis and clitoris – shows similarities with the external genitalia of other amniotes prior to sexual differentiation. Many genes and enhancers show a common role in both the limbs and the external genitalia, and disruption of these loci can cause aberrant phenotypes in both structures. Among these shared limb-genital genes is Isl1. The Isl1 gene encodes a homeodomain transcription factor that is required for initiation of the hindlimb bud and for normal GT development. This study uses a combination of RNA-seq, ChIP-seq, and comparative genomics to identify potential targets of ISL1 during both hindlimb initiation and GT outgrowth. ChIP-seq data from mouse, chick, and other species reveals targets that are likely conserved from the last common ancestor of amniotes. A subset of ISL1 targets are shared between the hindlimb and the external genitalia, supporting the hypothesis that aspects of phallus development were coopted from the limb gene regulatory network. This systematic investigation of ISL1 transcriptional targets expands our knowledge of Isl1’s role in appendage development and generates further testable hypotheses concerning the establishment of these structures.
2025-04-04 | GSE202285 | GEO
Project description:Characterize the cellular diversity of the embryonic genital tubercle before sexual dimorphic morphogenesis in male and female mice.
2021-05-26 | GSE175498 | GEO
Project description:The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing urogenital system. The central thesis is straightforward. The combination of microdissected and laser capture microdissection (LCM) plus Microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here represents the gene expression profiles of the embryonic day 14 genital tubercle of the male and the female. The genital tubercle region from E14 (TS22) FVB/N males and females were microdissected and total RNA isolated for gene expression analysis using the Affymetrix MOE430 microarray chip.
2012-12-04 | E-GEOD-42688 | biostudies-arrayexpress
Project description:To identify regulatory targets of the transcription factor Isl1 in the developing mouse genitalia, we performed ChIP-Seq using an anti-ISL1 rabbit monoclonal antibody on pooled chromatin isolated from multiple E14.5 mouse embryonic genital tubercles (GT). Our analysis identified more than 7,054 genomic regions enriched in both of two replicates. The majority of these binding sites are located more than 5 kb from the closest annotated transcriptional start site (TSS), with nearly one third of the binding sites more than 50kb away from the nearest TSS. A de novo motif search using HOMER demonstrated that GT Isl1 ChIP-seq peaks are enriched for a motif that matches the consensus sequence bound by Isl1 in other tissues. When compared to active enhancers in the GT identified using H3K27ac ChIP-Seq, we found that Isl1 binding sites are strongly enriched in the GT compared to other embryonic tissues. Further analysis of the location of Isl1 peaks revealed a strong association with genes implicated in limb and urogenital development. We conclude that there is a strong association between Isl1 regulatory activity and genes involved in genital development.
2017-11-08 | GSE91082 | GEO
Project description:Single Cell RNA-Seq of the embryonic day 14.5 genital tubercle
| PRJNA732639 | ENA
Project description:The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing urogenital system. The central thesis is straightforward. The combination of microdissected and laser capture microdissection (LCM) plus Microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here represents the gene expression profiles of the embryonic day 14 genital tubercle of the male and the female.
2012-12-04 | GSE42688 | GEO
Project description:The hindlimb and external genitalia of present-day tetrapods are thought to derive from an ancestral common primordium that evolved to generate a wide diversity of structures adapted for efficient locomotion and mating in the ecological niche conquered by the species. We show that despite long evolutionary distance from the ancestral condition, the early primordium of the mouse external genitalia preserved the capacity to take hindlimb fates. In the absence of Tgfbr1, the pericloacal mesoderm generates an extra pair of hindlimbs at the expense of the external genitalia. It has been shown that the hindlimb and the genital primordia share many of their key regulatory factors. Tgfbr1 controls the response to those factors acting in a pioneer-like mode to modulate the accessibility status of regulatory elements that control the gene regulatory networks leading to the formation of genital or hindlimb structures. Our work uncovers a remarkable tissue plasticity with potential implications in the evolution of the hindlimb/genital area of tetrapods, and identifies a novel mechanism for Tgfbr1 activity that might also contribute to the control of other physiological or pathological processes.
2024-02-23 | GSE231592 | GEO
Project description:The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing urogenital system. The central thesis is straightforward. The combination of microdissected and laser capture microdissection (LCM) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here represents the gene expression profiles of the embryonic day 14 gential tubercle of the male. Experiment Overall Design: The genital tubercle region from an E14 (TS22) SMAA/EYFP males were microdissected and total RNA isolated for gene expression analysis using the Affymetrix MOE430 microarray chip.
2008-06-15 | E-GEOD-7903 | biostudies-arrayexpress
Project description:Understanding factors that drive development and function of the sinoatrial node (SAN) is crucial to development of potential therapies for sinus arrhythmias, including potential generation of biological pacemakers. Here, we identify a key cell autonomous role for the LIM homeodomain transcription factor ISL1 for survival, proliferation and function of pacemaker cells throughout development. Chromatin immunoprecipitation assays performed utilizing antibody to ISL1 in chromatin extracts from FACS purified SAN cells demonstrated that ISL1 directly binds genomic regions within several genes critical for normal pacemaker function, including subunits of the L-type calcium channel, Ank2, and Tbx3. Other genes implicated in abnormal heart rhythm in humans were also direct downstream targets of ISL1 in SAN cells. Our studies represent the first in vivo ChIP-seq studies for SAN cells which provide a basis for further exploration of factors critical to SAN formation and function and highlight the potential for utilization of ISL1 in combination with other SAN transcription factors for generating pacemaker cells for therapy or drug screening purposes. ISL1 ChIP-seq profiling was performed in Hcn4-H2BGFP SAN cells purified from neonatal hearts.
2015-07-23 | E-GEOD-68974 | biostudies-arrayexpress