ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2021
Comparative genomic analysis of human GLI2 locus using slowly evolving fish revealed the ancestral gnathostome set of early developmental enhancers.
Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 5 citations in OpenAlex.
- Evolutionary pathway and genetic mechanisms of fin-to-limb transition in vertebrates.Frontiers in cell and developmental biology · 2026Review
- The combinatorial binding syntax of transcription factors in forebrain-specific enhancers.Biology open · 2025Article
- Cis-regulatory control of mammalian Trps1 gene expression.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2024Article
- Identification of ancestral gnathostome Gli3 enhancers with activity in mammals.Development, growth & differentiation · 2024Article
- Comparative genomic analysis of human GLI2 locus using slowly evolving fish revealed the ancestral gnathostome set of early developmental enhancers.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
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Abstract
backgroundThe zinc finger-containing transcription factor Gli2, is a key mediator of Hedgehog (Hh) signaling and participates in embryonic patterning of various organs including the central nervous system (CNS) and limbs. Abnormal expression of Gli2 can impede the transcription of Hh target genes through disruption of proper balance between Gli2 and Gli3 functions. Therefore, delineation of enhancers that are required for complementary roles of Glis would allow the interrogation of those pathogenic variants that cause gene dysregulation, and a corresponding abnormal phenotype. Previously, we reported tissue-specific enhancers for Gli family including Gli2 through direct tetrapod-teleost comparisons.
resultsHere, we employed the sequence alignments of slowly evolving spotted gar and elephant shark and have identified six novel conserved noncoding elements in human GLI2 containing locus. Zebrafish-based transgenic assays revealed that combined action of these autonomous CNEs reflects many aspects of Gli2 specific endogenous transcriptional activity, including CNS and pectoral fins.
conclusionTaken together with our previous findings, this study suggests that Hh-signaling controlled deployment of Gli2 activity in embryonic patterning arose in the common ancestor of gnathostomes. These GLI2 specific cis-regulatory modules will help to identify DNA variants that probably reside outside of coding intervals and are associated with congenital anomalies.
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