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Nkx genes are essential for maintenance of ventricular identity.

ABSTRACT: Establishment of specific characteristics of each embryonic cardiac chamber is crucial for development of a fully functional adult heart. Despite the importance of defining and maintaining unique features in ventricular and atrial cardiomyocytes, the regulatory mechanisms guiding these processes are poorly understood. Here, we show that the homeodomain transcription factors Nkx2.5 and Nkx2.7 are necessary to sustain ventricular chamber attributes through repression of atrial chamber identity. Mutation of nkx2.5 in zebrafish yields embryos with diminutive ventricular and bulbous atrial chambers. These chamber deformities emerge gradually during development, with a severe collapse in the number of ventricular cardiomyocytes and an accumulation of excess atrial cardiomyocytes as the heart matures. Removal of nkx2.7 function from nkx2.5 mutants exacerbates the loss of ventricular cells and the gain of atrial cells. Moreover, in these Nkx-deficient embryos, expression of vmhc, a ventricular gene, fades, whereas expression of amhc, an atrial gene, expands. Cell-labeling experiments suggest that ventricular cardiomyocytes can transform into atrial cardiomyocytes in the absence of Nkx gene function. Through suggestion of transdifferentiation from ventricular to atrial fate, our data reveal a pivotal role for Nkx genes in maintaining ventricular identity and highlight remarkable plasticity in differentiated myocardium. Thus, our results are relevant to the etiologies of fetal and neonatal cardiac pathology and could direct future innovations in cardiac regenerative medicine.

SUBMITTER: Targoff KL

PROVIDER: S-EPMC3787760 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Nkx genes are essential for maintenance of ventricular identity.

Targoff Kimara L KL Colombo Sophie S George Vanessa V Schell Thomas T Kim Seok-Hyung SH Solnica-Krezel Lilianna L Yelon Deborah D

Development (Cambridge, England) 20130911 20

Establishment of specific characteristics of each embryonic cardiac chamber is crucial for development of a fully functional adult heart. Despite the importance of defining and maintaining unique features in ventricular and atrial cardiomyocytes, the regulatory mechanisms guiding these processes are poorly understood. Here, we show that the homeodomain transcription factors Nkx2.5 and Nkx2.7 are necessary to sustain ventricular chamber attributes through repression of atrial chamber identity. Mu ...[more]

PMID: 24026123

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Project description:BackgroundIdentifying as someone who engages in health promoting behaviors like healthy eating and exercising may be associated with sustained engagement in those behaviors, but reliable and valid instruments are needed to improve the rigor of this research. Two studies were conducted to (1) examine the psychometric properties of a four-item exerciser identity measure (4-EI) and an adapted healthy-eater identity measure (4-HEI) and (2) examine differences in identity strengths across categories of weight loss success.MethodsData from 1,709 community dwelling adults in the International Weight Control Registry (IWCR) were used. A random half of the sample was used to assess the proposed unidimensional factor structure of the 4-EI and 4-HEI and examine convergent and discriminant validity using Spearman rank-order correlations. One-way ANOVA was used in the other random half of the sample to compare 4-EI and 4-HEI scores (-3 to + 3) across three self-defined weight loss categories ('Successful', 'Regain', and 'Unsuccessful') and those maintaining ≥ 5% weight loss for > 1 year vs. not.ResultsResults support the unidimensional factor structure with all four items (eigenvalue scores > 2.89) as well as convergent and discriminant validity for both measures. Exercise identity was strongly correlated with self-reported physical activity (r (735) = 0.52, p <.001) and measures of autonomous motivation. Healthy eating identity was moderately correlated with cognitive restraint in eating (r (744) = 0.42, p <.001) and other measures predictive of eating behavior. 4-EI and 4-HEI are stronger in Successful (4-EI: M = 0.90, SD = 1.77; 4-HEI: M = 1.56 SD = 1.37) vs. Regain (4-EI: M=-0.18, SD = 1.68; 4-HEI: M =.57, SD = 1.48) and Unsuccessful (4-EI:M=-0.28, SD = 1.62; 4-HEI: M = 0.51, SD = 1.33) and those maintaining ≥ 5% weight loss (4-EI:M = 0.47, SD = 1.78; 4-HEI: M = 1.13, SD = 1.49) vs. not (4-EI:M=-0.27, SD = 1.66; 4-HEI: M = 0.53, SD = 1.47), p's < 0.001.ConclusionsThe 4-EI and 4-HEI have acceptable psychometric properties and can advance understanding of the role of identity in exercise and dietary behaviors and weight loss maintenance.Trial registrationThe parent observational study, International Weight Control Registry (IWCR), for these sub-studies is registered in ClinicalTrials.gov (NCT04907396).

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Nkx genes are essential for maintenance of ventricular identity.

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Nkx genes are essential for maintenance of ventricular identity.

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