The Cardiac Neural Crest Cells in Heart Development and Congenital Heart Defects

Abstract

The neural crest (NC) is a multipotent and temporarily migratory cell population stemming from the dorsal neural tube during vertebrate embryogenesis. Cardiac neural crest cells (NCCs), a specified subpopulation of the NC, are vital for normal cardiovascular development, as they significantly contribute to the pharyngeal arch arteries, the developing cardiac outflow tract (OFT), cardiac valves, and interventricular septum. Various signaling pathways are shown to orchestrate the proper migration, compaction, and differentiation of cardiac NCCs during cardiovascular development. Any loss or dysregulation of signaling pathways in cardiac NCCs can lead to abnormal cardiovascular development during embryogenesis, resulting in abnormalities categorized as congenital heart defects (CHDs). This review focuses on the contributions of cardiac NCCs to cardiovascular formation, discusses cardiac defects caused by a disruption of various regulatory factors, and summarizes the role of multiple signaling pathways during embryonic development. A better understanding of the cardiac NC and its vast regulatory network will provide a deeper insight into the mechanisms of the associated abnormalities, leading to potential therapeutic advancements.

Systematic review of cardiovascular neurocristopathy—contemporary insights and future perspectives

“…During gastrulation, CNC cells are induced from the dorsal region of the neural plate border, orchestrated by various regulatory pathways such as Bmp, Wnt, Notch, and, more recently recognized, Hippo ( Figure 4 ) ( 37 ).…”

“…Varadkar and colleagues ( 43 ) discovered that Notch2 is required for proper NC-derived aortic and pulmonary smooth muscle formation and disrupting Notch2 in post-migratory CNC cells with the Pax3-Cre driver results in narrowed OFT and OFT arteries (aorta and pulmonary) in E17.5 mouse embryos, indicating a cell-autonomous role for Notch2 in CNC cells. However, there is a lack of studies that look into how Notch manipulation contributes to CNC-derived heart development ( 37 ).…”

Differentiation and quality control of smooth muscle cells from human pluripotent stem cells via the neural crest lineage

“…Neural crest lineage cells are also present in areas of the heart, and being able to identify and recapitulate such specific cell lineages in vitro could be significant in investigating mechanisms in non-vascular diseases (Erhardt et al, 2021).…”

Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis

“…Cardiovascular development is a complex developmental process in which multiple cell types are involved [ 357 ]. Over the last decades, our understanding of the cellular contribution to the developing heart has been enormous, particularly dissecting the deployment of distinct heart fields to the nascent cardiac tube [ 358 , 359 ] as well as the extracardiac contributions emanating from the epicardium and the cardiac neural crest [ 227 , 360 ]. Similarly, our understanding of molecular cascades governing these morphogenetic events has been equally impressive, by dissecting the functional role of multiple growth factors and transcription factors during cardiogenesis [ 357 ].…”