Nodal Signaling and Congenital Heart Defects

Abstract

Nodal is a TGF-β family member ligand that is critical for early embryonic patterning in vertebrates.

High cardiomyocyte diversity in human early prenatal heart development

“…Both FGF and VEGF ligands acted through various receptors at colocalized cells, as did TNF, BMP, NPPA, and thyrosine kinase AXL, affecting the smooth muscle, fibroblasts, and endothelium. Extracellular instructive signals affecting exosome-enriched CMs included L-R crosstalk with the nodal morphogen TGF-beta pair LEFTY2_TDGF1 (Barnes and Black, 2016; Behrens et al, 2012; Noseda et al, 2011) and CD47_SIRPA, suggesting that these CMs are at an early stage of development. SIPRA is a cell surface receptor expressed at cardiomyocyte progenitors and early cardiomyocytes (Dubois et al, 2011; Skelton et al, 2014).…”

Potential roles of GATA binding protein 5 in cardiovascular diseases

“…Notably, GDF1 directly interacts with Nodal growth differentiation factor (Nodal) to form a GDF1-Nodal heterodimer, which significantly increases the activity of Nodal (Tanaka et al, 2007). Nodal and its family members are important signal molecules for heart development ( Barnes and Black, 2016;David and Massagué, 2018;Mohapatra et al, 2009). Therefore, a GATA5/cx36.7/NKX2-5/GDF1/Nodal signal pathway provides another way for GATA5 to participate in the occurrence of various congenital heart diseases (Fig.…”

“…GATA5 mediates the occurrence and development of cardiovascular disease and cancer. For example, the Nodal signaling pathway regulated by GATA5 is not only related to a series of congenital defects, including CHD (Barnes and Black, 2016), but is also involved in maintaining the survival, proliferation, invasion and self-renewal of cancer cell lines (Kalyan et al, 2017;Kirsammer et al, 2014;Wei and Wang, 2018). (3) Epigenetic modifications such as DNA methylation represent the molecular substrate for detrimental environmental stimuli and may lead to cardiovascular disease initiation including CHD (Lorenzen et al, 2012;Vallaster et al, 2012).…”

The Functions of Long Non-Coding RNA during Embryonic Cardiovascular Development and Its Potential for Diagnosis and Treatment of Congenital Heart Disease

“…As an example of this process, we will here discuss patterning of left-right identity in cardiogenic precursors within the lateral plate mesoderm (LPM). This patterning process is critical for many aspects of subsequent cardiovascular morphogenesis, including asymmetric morphogenesis of the atria and vasculature, and its disruption is one of the causes of CHD [8,47,48]. The same pathway patterns precursors of the lung, resulting in its asymmetric development, and of the dorsal mesentery, asymmetric growth of which regulates looping of the gut.…”