Identification of TBX3 and shared HAND2-TBX3 target genes in early mouse limb buds
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ABSTRACT:
PROVIDER: PRJNA791643 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17311424.fastq.gz | Fastqsanger.gz | |||
| SRR17311425.fastq.gz | Fastqsanger.gz | |||
| SRR17311426.fastq.gz | Fastqsanger.gz | |||
| SRR17311427.fastq.gz | Fastqsanger.gz | |||
| SRR17311428.fastq.gz | Fastqsanger.gz |
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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).
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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).
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Project description:Identification of TBX3 and shared HAND2-TBX3 target genes in early mouse limb buds [ChIP-seq]
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Project description:Identification of TBX3 and shared HAND2-TBX3 target gene in early mouse limb buds [RNA-seq]
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:The bHLH transcriptional regulator HAND2 performs essential functions during development of the embryonic limb, heart and branchial arches, however, its genomic target regions remained largely unkown. Here, we uncover the range of candidate HAND2 target cis-regulatory modules in the major Hand2 expressing embryonic tissues during midgestation and focus on the transcriptional networks controlled by HAND2 in the developing limb. Our functional and genetic analysis reveals that in the early limb mesenchyme HAND2 directly regulates the expression of several transcription factors involved in the morphogenesis of limb proximal skeletal elements. In addition, HAND2 operates as a key factor in the establishment of anterior and posterior compartments, partly through direct binding to a Gli3 cis-regulatory module. Furthermore, HAND2 refines the posterior boundary of Gli3 expression domain through a relay mechanism mediated by Tbx3. These HAND2-dependent regulatory interactions are required to set the boundaries defining the localized expression of the Shh organizer region, which allows progression of distal limb outgrowth.
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Project description:During development cell fates are specified by tightly controlled gene expression programs. PBX TALE transcription factors control gene regulatory networks (GRN) that direct vertebrate tissue patterning and organ morphogenesis. How PBX1/2 proteins achieve context-specific functions, despite widespread embryonic Pbx expression, remains elusive. In mouse limbs, mesenchymal-specific loss of PBX1/2 or of the limb regulator HAND2 results in strikingly similar phenotypes, suggesting that PBX1/2- and HAND2-dependent programs converge to control limb development. To investigate this scenario using the murine hindlimb model, we combined tissue-specific and temporally controlled mutagenesis to multi-omics approaches on dissected hindlimb buds. This resulted in the reconstruction of a GRN that is collaboratively directed by PBX1/2-HAND2, demonstrating that Pbx1-Hand2 genetically interact in vivo during pentadactylous hindlimb patterning, with PBX1 concomitantly acting as an upstream regulator of Hand2. At organismal-level resolution the GRN is active within restricted subsets of posterior-proximal hindlimb mesenchymal cells, wherein Pbx1/2 and Hand2 are co-expressed with their target genes. Profiling the binding of Pbx1 and Hand2 genome-wide across multiple tissues revealed that HAND2 can act selectively on a subset of PBX-bound regions to impart limb patterning functionality. Our research elucidates mechanisms on the limb-specific activities of PBX1/2, while informing general principles by which promiscuous transcription factors cooperate with select cofactors to instruct distinct developmental programs.
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Project description:During development cell fates are specified by tightly controlled gene expression programs. PBX TALE transcription factors control gene regulatory networks (GRN) that direct vertebrate tissue patterning and organ morphogenesis. How PBX1/2 proteins achieve context-specific functions, despite widespread embryonic Pbx expression, remains elusive. In mouse limbs, mesenchymal-specific loss of PBX1/2 or of the limb regulator HAND2 results in strikingly similar phenotypes, suggesting that PBX1/2- and HAND2-dependent programs converge to control limb development. To investigate this scenario using the murine hindlimb model, we combined tissue-specific and temporally controlled mutagenesis to multi-omics approaches on dissected hindlimb buds. This resulted in the reconstruction of a GRN that is collaboratively directed by PBX1/2-HAND2, demonstrating that Pbx1-Hand2 genetically interact in vivo during pentadactylous hindlimb patterning, with PBX1 concomitantly acting as an upstream regulator of Hand2. At organismal-level resolution the GRN is active within restricted subsets of posterior-proximal hindlimb mesenchymal cells, wherein Pbx1/2 and Hand2 are co-expressed with their target genes. Profiling the binding of Pbx1 and Hand2 genome-wide across multiple tissues revealed that HAND2 can act selectively on a subset of PBX-bound regions to impart limb patterning functionality. Our research elucidates mechanisms on the limb-specific activities of PBX1/2, while informing general principles by which promiscuous transcription factors cooperate with select cofactors to instruct distinct developmental programs.
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Project description:During development cell fates are specified by tightly controlled gene expression programs. PBX TALE transcription factors control gene regulatory networks (GRN) that direct vertebrate tissue patterning and organ morphogenesis. How PBX1/2 proteins achieve context-specific functions, despite widespread embryonic Pbx expression, remains elusive. In mouse limbs, mesenchymal-specific loss of PBX1/2 or of the limb regulator HAND2 results in strikingly similar phenotypes, suggesting that PBX1/2- and HAND2-dependent programs converge to control limb development. To investigate this scenario using the murine hindlimb model, we combined tissue-specific and temporally controlled mutagenesis to multi-omics approaches on dissected hindlimb buds. This resulted in the reconstruction of a GRN that is collaboratively directed by PBX1/2-HAND2, demonstrating that Pbx1-Hand2 genetically interact in vivo during pentadactylous hindlimb patterning, with PBX1 concomitantly acting as an upstream regulator of Hand2. At organismal-level resolution the GRN is active within restricted subsets of posterior-proximal hindlimb mesenchymal cells, wherein Pbx1/2 and Hand2 are co-expressed with their target genes. Profiling the binding of Pbx1 and Hand2 genome-wide across multiple tissues revealed that HAND2 can act selectively on a subset of PBX-bound regions to impart limb patterning functionality. Our research elucidates mechanisms on the limb-specific activities of PBX1/2, while informing general principles by which promiscuous transcription factors cooperate with select cofactors to instruct distinct developmental programs.
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