Similar Datasets
Project description:ChIP-seq is combined with RNA-seq analysis to identify the TBX3 and HAND2 target genes during mouse limb bud development. This analysis identifies the DEGs and direct transcriptional targets of HAND2 and TBX3 during the early determinative period critical to establishment of limb axis polarity and the SHH signaling center in the posterior limb bud mesenchyme. In particular, bioinformatics analysis identifies the target gene networks that are co-regulated by both TBX3 and HAND2 transcription factors in the limb bud mesenchyme. A significant fraction of the target genes identified are required for normal limb bud development and their spatio-temporal expression patterns are changed in mutant limb buds at early stages. This project was supported by SNSF Grant 310030_184734 to Rolf Zeller (project partner: Aimée Zuniga).
2023-12-31 | GSE192484 | GEO
Project description:ChIP-seq is combined with RNA-seq analysis to identify the TBX3 and HAND2 target genes during mouse limb bud development. This analysis identifies the DEGs and direct transcriptional targets of HAND2 and TBX3 during the early determinative period critical to establishment of limb axis polarity and the SHH signaling center in the posterior limb bud mesenchyme. In particular, bioinformatics analysis identifies the target gene networks that are co-regulated by both TBX3 and HAND2 transcription factors in the limb bud mesenchyme. A significant fraction of the target genes identified are required for normal limb bud development and their spatio-temporal expression patterns are changed in mutant limb buds at early stages. This project was supported by SNSF Grant 310030_184734 to Rolf Zeller (project partner: Aimée Zuniga).
2023-12-31 | GSE192485 | GEO
Project description:Identification of TBX3 and shared HAND2-TBX3 target genes in early mouse limb buds
| PRJNA791643 | ENA
Project description:Identification of TBX3 and shared HAND2-TBX3 target genes in early mouse limb buds [ChIP-seq]
| PRJNA791649 | ENA
Project description:Identification of TBX3 and shared HAND2-TBX3 target gene in early mouse limb buds [RNA-seq]
| PRJNA791648 | ENA
Project description:Anterior-posterior (A-P) patterning of the vertebrate limb is controlled by sonic hedgehog (SHH) signaling, and the precise restriction of Shh expression to the posterior limb bud is essential for its polarizing effect. Fibroblast growth factor (FGF) signaling, a key control of proximal-distal (P-D) limb outgrowth, is known to promote Shh expression in the posterior limb bud. Here, we show that conditional knockout of the FGF-activated transcription factor genes Etv4 and Etv5 in mouse led to ectopic Shh expression in the anterior limb bud and a preaxial polydactyly (PPD) skeletal phenotype. These unexpected results suggest that ETV4 and ETV5 act downstream of FGF signaling to inhibit Shh expression in the anterior limb bud. This finding elucidates a novel aspect of the mechanism coordinating limb development along the A-P and P-D axes.
| S-EPMC3541528 | biostudies-literature
Project description:Deficiency of the human short stature homeobox-containing gene (SHOX) has been identified in several disorders characterized by reduced height and skeletal anomalies such as Turner syndrome, Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia as well as isolated short stature. SHOX acts as a transcription factor during limb development and is expressed in chondrocytes of the growth plates. Although highly conserved in vertebrates, rodents lack a SHOX orthologue. This offers the unique opportunity to analyze the effects of human SHOX expression in transgenic mice. We have generated a mouse expressing the human SHOXa cDNA under the control of a murine Col2a1 promoter and enhancer (Tg(Col2a1-SHOX)). SHOX and marker gene expression as well as skeletal phenotypes were characterized in two transgenic lines. No significant skeletal anomalies were found in transgenic compared to wildtype mice. Quantitative and in situ hybridization analyses revealed that Tg(Col2a1-SHOX), however, affected extracellular matrix gene expression during early limb development, suggesting a role for SHOX in growth plate assembly and extracellular matrix composition during long bone development. For instance, we could show that the connective tissue growth factor gene Ctgf, a gene involved in chondrogenic and angiogenic differentiation, is transcriptionally regulated by SHOX in transgenic mice. This finding was confirmed in human NHDF and U2OS cells and chicken micromass culture, demonstrating the value of the SHOX-transgenic mouse for the characterization of SHOX-dependent genes and pathways in early limb development.
| S-EPMC4041798 | biostudies-literature
Project description:Limb patterning relies in large part on the function of the Hox family of developmental genes. While the differential expression of Hox genes shifts from the anterior-posterior (A-P) to the proximal-distal (P-D) axis around embryonic day 11 (E11), whether this shift coincides with a more global change of A-P to P-D patterning program remains unclear. By performing and analyzing the transcriptome of the developing limb bud from E10.5 to E12.5, at single-cell resolution, we have uncovered transcriptional trajectories that revealed a general switch from A-P to P-D genetic program between E10.5 and E11.5. Interestingly, all the transcriptional trajectories at E10.5 end with cells expressing either proximal or distal markers suggesting a progressive acquisition of P-D identity. Moreover, we identified three categories of genes expressed in the distal limb mesenchyme characterized by distinct temporal expression dynamics. Among these are Hoxa13 and Hoxd13 (Hox13 hereafter), which start to be expressed around E10.5, and importantly the binding of the HOX13 factors was observed within or in the neighborhood of several of the distal limb genes. Our data are consistent with previous evidence suggesting that the transition from the early/proximal to the late/distal transcriptome of the limb mesenchyme largely relies on HOX13 function. Based on these results and the evidence that HOX13 factors restrict Hoxa11 expression to the proximal limb, in progenitor cells of the zeugopod, we propose that HOX13 act as a key determinant of P-D patterning.
| S-EPMC7768367 | biostudies-literature
Project description:The key molecular interactions governing vertebrate limb bud development are a paradigm for studying the mechanisms controlling progenitor cell proliferation and specification during vertebrate organogenesis. However, little is known about the cellular heterogeneity of the mesenchymal progenitors in early limb buds that ultimately contribute to the chondrogenic condensations prefiguring the skeleton. We combined flow cytometric and transcriptome analyses to identify the molecular signatures of several distinct mesenchymal progenitor cell populations present in early mouse forelimb buds. In particular, jagged 1 (JAG1)-positive cells located in the posterior-distal mesenchyme were identified as the most immature limb bud mesenchymal progenitors (LMPs), which crucially depend on SHH and FGF signaling in culture. The analysis of gremlin 1 (Grem1)-deficient forelimb buds showed that JAG1-expressing LMPs are protected from apoptosis by GREM1-mediated BMP antagonism. At the same stage, the osteo-chondrogenic progenitors (OCPs) located in the core mesenchyme are already actively responding to BMP signaling. This analysis sheds light on the cellular heterogeneity of the early mouse limb bud mesenchyme and on the distinct response of LMPs and OCPs to morphogen signaling.
| S-EPMC6550019 | biostudies-literature
Project description:Transcriptional responses to the Hedgehog (HH) signaling pathway are primarily modulated by GLI repression in the mouse limb. Previous studies suggested a role for the BAF chromatin remodeling complex in mediating GLI repression. Consistent with this possibility, the core BAF complex protein SMARCC1 is present at most active limb enhancers including the majority of GLI enhancers. However, in contrast to GLI repression which reduces chromatin accessibility, SMARCC1 maintains chromatin accessibility at most enhancers, including those bound by GLI. Moreover, SMARCC1 binding at GLI-regulated enhancers occurs independently of GLI3. Consistent with previous studies, some individual GLI target genes are mis-regulated in Smarcc1 conditional knockouts, though most GLI target genes are unaffected. Moreover, SMARCC1 is not necessary for mediating constitutive GLI repression in HH mutant limb buds. We conclude that SMARCC1 does not mediate GLI3 repression, which we propose utilizes alternative chromatin remodeling complexes.
| S-EPMC9934545 | biostudies-literature