Neural crest and cardiovascular development: A 20‐year perspective

Abstract

We propose that the cardiac neural crest exists as part of a larger cardiocraniofacial morphogenetic field and describe several human syndromes that result from abnormal development of this field.

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

“…Highly migratory NCCs are a multipotent cell population that possesses a capability to differentiate not only into neuronal cells, such as peripheral neurons and glia, but also into non-neuronal cells such as melanocytes, smooth muscle, bone, and cartilage, making crucial contributions to the development of an astounding array of tissues or organs (Hutson and Kirby, 2003;Schmidt and Patel, 2005). Therefore, defective NC development results in a diverse range of congenital disorders, including craniofacial and cardiovascular malformations (Hutson and Kirby, 2003;Farlie et al, 2004). Cleft palate and cardiac outflow tract defects of Pnn 3f/3f mice thus suggest the maldevelopment of NCCs in Pnn hypomorphic mice.…”

“…Instead, Pnn hypomorphs exhibited a complex phenotype. Intriguingly, all of these phenotypes-vertebral patterning (Ikeya and Takada, 2001;Aulehla et al, 2003), dorsal dermis development (Olivera-Martinez et al, 2001, BAT formation (Atit et al, 2006), and palate and outflow tract development (Hamblet et al, 2002;Hutson and Kirby, 2003;Schmidt and Patel, 2005)-have been observed in mice having defects in Wnt/␤-catenin signaling. This finding raised an interesting possibility that PNN might be involved in the regulation of Wnt/␤-catenin signaling during mouse development.…”

“…Pnn 3f/3f mice also displayed several defects that implicate perturbation in the development of neural crest cells (NCCs), which originate from neuroepithelium at the dorsolateral margins of the neural tube, migrate and differentiate into various cell types and tissues including craniofacial and cardiac outflow structures (Hutson and Kirby, 2003;Schmidt and Patel, 2005). Approximately 30% of Pnn 3f/3f mice showed cleft palate (Fig.…”

“…5C,D) associated with outflow tract defects ( Fig. 5E-G; Table 2), such as double outlet right ventricle (DORV), transposition of the great arteries (TGA), or persistent truncus arteriosus (PTA), which have been routinely observed in animals with defective cardiac NCCs (Hutson and Kirby, 2003).…”

Cell biology of embryonic migration

“…Waardenburg's syndrome, characterized by abnormal pigmentation, results from the impaired migration of neural crest cells that give rise to the melanocytes of the skin (Tachibana et al, 2003;Tucker, 2004). Other human syndromes, including Alagille, Carpenter, CHARGE, Ivemark, and Leopard/Noonan syndromes, result in abnormalities that suggest impairments of the neural crest migration, with known or unknown molecular reasons (Hutson and Kirby, 2003). Increasing molecular understanding of the embryonic migratory mechanisms provides means for the development of new therapies for these diseases in humans.…”