Advanced - Molecular Development
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In attempts to determine the molecular mechanisms controlling heart development, scientists have focussed on early cardiomyocyte development including the cellular movement of cardiomyocyte progenitors and the signaling mechanisms that regulate cardiomyogenesis from the blastula to gastrula stages as well as the morphological changes that occur later in development such as looping and septation. Some of the molecular and genetic factors regulating cardiac development have been previously described in this module in the aspect of development they pertain to. The following diagram provides an overview to the steps in cardiac development and the important associated genes, transcription factors and signalling molecules. Underneath this is a list of some of the predominant molecular pathways contributing to cardiac development.
- Nk family transcription factors are expressed in all animals with contractile vascular cells and hence are crucial for myocardial development; Nkx2.5 is specifically required for left ventricular chamber development.
- Gata family transcription factors interact with Nk factors to promote differentiation of cardiomyocytes, smooth muscle cells and endoderm; Gata4 regulates myocardial expression and is required for fusion of the heart tubes in the ventral midline; Gata5 is required for endocardial differentiation.
- T-box genes play an important role in cardiac morphogenesis; Tbx1 may play a role in neural crest proliferation/function; Tbx2 plays a significant role in chamber specification; Tbx5 is required for atrial septation.
- Pitx2 is a left-sided transcription factor that controls normal cardiac morphogenesis by regulating cell proliferation.
- BMP (Bone morphogenetic protein) particularly Bmp2 is expressed in cardiogenic mesoderm and is important for specification and myocardial differentiation.
- WNT signalling inhibition promotes cardiogenesis in the cardiogenic mesoderm.
- FGF (Fibroblast growth factor) acts alongside Bmp to allow for myocardial differentiation. Fgf8 is expressed in cardiogenic mesoderm and hence allows for cardiac specification.
- Notch signalling establishes sub-populations within the cardiogenic mesoderm by regulating asymmetric cell division. Notch also has an inhibitory effect on myocardial differentiation.
- Cripto mediates Nodal signalling to allow for myocardial differentiation.
- TBX T-box proteins act as transcription factors regulating the expression of other developmental genes.
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