Evidence map›Paper›PMID 41392312›Full record

ArticleEvoDevo2025

Functional divergence of Tbx2a and Tbx2b in zebrafish heart development.

Maliha Tasnim, Kaitlyn A Robinson, Connor B Ward, Logan P Melling, Hannah N Jenkins, Preston Wahlquist, Jared Elison, John C Price, Jonathon T Hill

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Article in EvoDevo, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Maliha TasnimDepartment of Cell Biology and Physiology, Brigham Young University, 701 E University Pkwy, LSB 4005, Provo, UT, 84602, USA.
Kaitlyn A RobinsonDepartment of Cell Biology and Physiology, Brigham Young University, 701 E University Pkwy, LSB 4005, Provo, UT, 84602, USA.
Connor B WardDepartment of Cell Biology and Physiology, Brigham Young University, 701 E University Pkwy, LSB 4005, Provo, UT, 84602, USA.
Logan P MellingDepartment of Cell Biology and Physiology, Brigham Young University, 701 E University Pkwy, LSB 4005, Provo, UT, 84602, USA.
Hannah N JenkinsDepartment of Cell Biology and Physiology, Brigham Young University, 701 E University Pkwy, LSB 4005, Provo, UT, 84602, USA.
Preston WahlquistDepartment of Cell Biology and Physiology, Brigham Young University, 701 E University Pkwy, LSB 4005, Provo, UT, 84602, USA.
Jared ElisonDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
John C PriceDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Jonathon T HillDepartment of Cell Biology and Physiology, Brigham Young University, 701 E University Pkwy, LSB 4005, Provo, UT, 84602, USA. jhill@byu.edu.

Funding

Biochemical Consequences of Regiospecific Metabolic Bias in the BrainR01AG066874 · NIA · BRIGHAM YOUNG UNIVERSITY · PI PRICE, JOHN C. · 2020 to 2024
$3.0M
Eunice Kennedy Shriver National Institute of Child Health and Human Development R15HD098969NIA NIH HHS R01AG066874
6 · The paper itself

Abstract

Congenital Heart Disease (CHD) is currently the most common birth defect, affecting approximately 1% of live births. Understanding the genetic mechanisms underlying CHD is crucial for developing effective interventions. This paper explores the functional and evolutionary roles of the T-box transcription factors Tbx2a and Tbx2b in zebrafish heart development. Functional studies in zebrafish demonstrated that both homozygous and heterozygous mutations in tbx2a and tbx2b result in heart looping defects, challenging the assumption of their redundancy and indicating unique, non-overlapping functions essential for cardiac development. The observed phenotypic variability in heterozygous mutants suggests a complex interplay between these genes and highlights the sensitivity of cardiac development to precise gene dosage. Utilizing advanced bioinformatics techniques, we reconstructed the ancestral sequences of these genes to understand their evolutionary trajectory and functional divergence. Our analysis revealed strong evolutionary conservation of the T-box DNA-binding domain in Tbx2a and Tbx2b, suggesting that both proteins remain constrained to recognize the same core cis-regulatory elements. This conservation implies that their ability to bind essential cardiac target genes is functionally indispensable and under strong purifying selection. We observed unique and shared amino acid substitutions, indicating potential adaptive changes and conserved functions. Given their highly conserved DNA-binding domains, we hypothesized that Tbx2a and Tbx2b interact with different nuclear factors to regulate distinct sets of genes. Mass spectrometry-based proteomics provided insights into the unique nuclear interactions of Tbx2a and Tbx2b, supporting the hypothesis of their functional divergence. Overall, this research offers new insights into the functional and evolutionary roles of Tbx2a and Tbx2b in heart development, with implications for understanding the genetic basis of CHD.

Indexed as

BioinformaticsCardiac developmentCongenital heart diseaseEvolutionary biologyFunctional genomicsGene duplicationT-box transcription factorsTbx2aTbx2bZebrafish

Identifiers

PMID41392312

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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.