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Chamber formation and morphogenesis in the developing mammalian heart
V M Christoffels1, P E Habets, D Franco
1Department of Anatomy & Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, 1105, The Netherlands.
Insights
This study challenges traditional views on cardiac chamber formation, proposing a two-step model for embryonic heart development. It reveals distinct molecular signatures guiding the specification of heart chambers during development.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Molecular Genetics
Background:
- The prevailing model suggests cardiac chambers arise segmentally along the heart tube's axis.
- Understanding the precise molecular mechanisms of heart chamber formation is crucial for developmental biology.
Purpose of the Study:
- To challenge the segmental primordia model of cardiac chamber formation.
- To propose and provide evidence for a novel two-step model of embryonic heart chamber development.
Main Methods:
- Spatial gene expression analysis of key developmental genes (e.g., ANF, SERCA, Irx5, Irx4, MLC2v, β-MHC).
- Correlating gene expression patterns with cardiac morphogenesis during embryonic development.
Main Results:
- Cardiac chambers form via a two-step process: initial linear heart tube polarity, followed by specialized myocardial specification.
- Ventricular myocardium specifies ventrally, while atrial myocardium forms caudally on laterodorsal surfaces.
- Specific transcription factors (Hand1, Irx4, Tbx5, Irx5) orchestrate heart compartmentalization.
Conclusions:
- The study proposes a revised model for embryonic heart chamber formation, emphasizing molecularly distinct myocardial specification.
- Gene expression patterns reveal polarity within the linear heart tube and specialized domains for chamber development.
- This work provides new insights into the transcriptional programs governing heart development and compartmentalization.
Abstract:
In this study we challenge the generally accepted view that cardiac chambers form from an array of segmental primordia arranged along the anteroposterior axis of the linear and looping heart tube. We traced the spatial pattern of expression of genes encoding atrial natriuretic factor, sarcoplasmic reticulum calcium ATPase, Chisel, Irx5, Irx4, myosin light chain 2v, and beta-myosin heavy chain and related these to morphogenesis. Based on the patterns we propose a two-step model for chamber formation in the embryonic heart. First, a linear heart forms, which is composed of "primary" myocardium that nonetheless shows polarity in phenotype and gene expression along its anteroposterior and dorsoventral axes. Second, specialized ventricular chamber myocardium is specified at the ventral surface of the linear heart tube, while distinct left and right atrial myocardium forms more caudally on laterodorsal surfaces. The process of looping aligns these primordial chambers such that they face the outer curvature. Myocardium of the inner curvature, as well as that of inflow tract, atrioventricular canal, and outflow tract, retains the molecular signature originally found in linear heart tube myocardium. Evidence for distinct transcriptional programs which govern compartmentalization in the forming heart is seen in the patterns of expression of Hand1 for the dorsoventral axis, Irx4 and Tbx5 for the anteroposterior axis, and Irx5 for the distinction between primary and chamber myocardium.