ArticleNature communications2023
A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Spaceborne and spaceborn: Physiological aspects of pregnancy and birth during interplanetary flight.Experimental physiology · 2026Review
- Targeting the PBX1-BCL2L1 axis as a therapeutic strategy in colorectal cancer.Cell death discovery · 2026Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Age-dependent differences in breast tumor microenvironment: challenges and opportunities for efficacy studies in preclinical models.Cell death and differentiation · 2025Article
- Unveiling the shared etiology between gastrointestinal disorders and valvular heart diseases through a genome-wide pleiotropy study.NPJ cardiovascular health · 2025Article
- PBX1 and PBX3 transcription factors regulate SHH expression in the Frontonasal Ectodermal Zone through complementary mechanisms.PLoS genetics · 2025Article
- Single-cell Transcriptomic Studies Unveil Potential Nodes of the Notochord Gene Regulatory Network.Integrative and comparative biology · 2024Review
- Integrated multi-omics analysis of PBX1 in mouse adult neural stem- and progenitor cells identifies a transcriptional module that functionally links PBX1 to TCF3/4.Nucleic acids research · 2024Article
- TBX3 is essential for establishment of the posterior boundary of anterior genes and upregulation of posterior genes together with HAND2 during the onset of limb bud development.Development (Cambridge, England) · 2024Article
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- PBX1: a TALE of two seasons-key roles during development and in cancer.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
Abstract
A lingering question in developmental biology has centered on how transcription factors with widespread distribution in vertebrate embryos can perform tissue-specific functions. Here, using the murine hindlimb as a model, we investigate the elusive mechanisms whereby PBX TALE homeoproteins, viewed primarily as HOX cofactors, attain context-specific developmental roles despite ubiquitous presence in the embryo. We first demonstrate that mesenchymal-specific loss of PBX1/2 or the transcriptional regulator HAND2 generates similar limb phenotypes. By combining tissue-specific and temporally controlled mutagenesis with multi-omics approaches, we reconstruct a gene regulatory network (GRN) at organismal-level resolution that is collaboratively directed by PBX1/2 and HAND2 interactions in subsets of posterior hindlimb mesenchymal cells. Genome-wide profiling of PBX1 binding across multiple embryonic tissues further reveals that HAND2 interacts with subsets of PBX-bound regions to regulate limb-specific GRNs. Our research elucidates fundamental principles by which promiscuous transcription factors cooperate with cofactors that display domain-restricted localization to instruct tissue-specific developmental programs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.