ArticleProceedings of the National Academy of Sciences of the United States of America2007
Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- The transcriptional repressor HEY2 regulates mitochondrial oxidative respiration to maintain cardiac homeostasis.Nature communications · 2025Article
- Smarce1 fine-tunes cardiomyocyte proliferation in the embryonic zebrafish heart.Frontiers in cell and developmental biology · 2025Article
- Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region.Cellular and molecular life sciences : CMLS · 2021Article
- The Gridlock transcriptional repressor impedes vertebrate heart regeneration by restricting expression of lysine methyltransferase.Development (Cambridge, England) · 2020Article
- Pbx4 limits heart size and fosters arch artery formation by partitioning second heart field progenitors and restricting proliferation.Development (Cambridge, England) · 2020Article
- Discovering small molecules as Wnt inhibitors that promote heart regeneration and injury repair.Journal of molecular cell biology · 2020Article
- Zebrafish models in cardiac development and congenital heart birth defects.Differentiation; research in biological diversity · 2012Review
- Discovering small molecules that promote cardiomyocyte generation by modulating Wnt signaling.Chemistry & biology · 2011Article
- The cardiovascular triad of dysfunctional angiogenesis.Translational stroke research · 2011Article
- Fli+ etsrp+ hemato-vascular progenitor cells proliferate at the lateral plate mesoderm during vasculogenesis in zebrafish.PloS one · 2011Article
- Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish.Developmental biology · 2008Article
- Fishing for the genetic basis of cardiovascular disease.Disease models & mechanismsReview
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Embryonic organs attain their final dimensions through the generation of proper cell number and size, but the control mechanisms remain obscure. Here, we establish Gridlock (Grl), a Hairy-related basic helix-loop-helix (bHLH) transcription factor, as a negative regulator of cardiomyocyte proliferative growth in zebrafish embryos. Mutations in grl cause an increase in expression of a group of immediate-early growth genes, myocardial genes, and development of hyperplastic hearts. Conversely, cardiomyocytes with augmented Grl activity have diminished cell volume and fail to divide, resulting in a marked reduction in heart size. Both bHLH domain and carboxyl region are required for Grl negative control of myocardial proliferative growth. These Grl-induced cardiac effects are counterbalanced by the transcriptional activator Gata5 but not Gata4, which promotes cardiomyocyte expansion in the embryo. Biochemical analyses show that Grl forms a complex with Gata5 through the carboxyl region and can repress Gata5-mediated transcription via the bHLH domain. Hence, our studies suggest that Grl regulates embryonic heart growth via opposing Gata5, at least in part through their protein interactions in modulating gene expression.
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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.