AI Article Synopsis
- BMP genes are essential for heart development, and this study focused on the effects of the BMP antagonist Noggin on this process.
- Persistent expression of Noggin in heart progenitor cells halted cardiac development at an early stage, leading to lower cell proliferation and increased cell death.
- The study highlights that BMP signaling is crucial for heart maturation and function, particularly in regulating cell growth and the development of contractile structures in the heart.
Article Abstract
Background: Multiple bone morphogenetic protein (BMP) genes are expressed in the developing heart from the initiation to late-differentiation stages, and play pivotal roles in cardiovascular development. In this study, we investigated the requirement of BMP activity in heart development by transgenic over-expression of extracellular BMP antagonist Noggin.
Results: Using Nkx2.5-Cre to drive lineage-restricted Noggin within cardiomyocyte progenitors, we show persistent Noggin arrests cardiac development at the linear heart stage. This is coupled with a significantly reduced cell proliferation rate, subsequent cardiomyocyte programmed cell death and reduction of downstream intracellular pSMAD1/5/8 expression. Noggin mutants exhibit reduced heartbeat which likely results in subsequent fully penetrant in utero lethality. Significantly, confocal and electron micrographic examination revealed considerably fewer contractile elements, as well as a lack of maturation of actin-myosin microfilaments. Molecular analysis demonstrated that ectopic Noggin-expressing regions in the early heart's pacemaker region, failed to express the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (Hcn4), resulting in an overall decrease in Hcn4 levels.
Conclusions: Combined, our results reveal a novel role for BMP signaling in the progression of heart development from the tubular heart stage to the looped stage by means of regulation of proliferation and promotion of maturation of the in utero heart's contractile apparatus and pacemaker.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344892 | PMC |
| http://dx.doi.org/10.1002/dvdy.24233 | DOI Listing |
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