Neural crest and normal development: A new perspective

Abstract

Several clinical syndromes, including the DiGeorge syndrome, are characterized by clusters of developmental defects of the heart and great vessels with structures derived from the embryonic pharyngeal apparatus including thymus and parathyroids. The connective tissue derivatives of neural crest are necessary for the normal development of these structures, and there is new experimental evidence that depletion of neural crest causes defects similar to these clinical syndromes. Therefore it is proposed that many of these syndromes are due to inappropriate development of neural crest. The implications of this hypothesis include the predictions 1) that asplenia and certain other anomalies have the same etiology, and 2) that it is possible to observe the effects of teratogenic agents upon a cellular population (neural crest) at the time when it is being altered, rather than waiting until definitive organs may be examined.

A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region.

“…Although the current consensus is that 330 many of these abnormalities may be the result of an interruption in developmental processes involving the cranial neural crest (Kirby and Bockman 1984;Lammer and Opitz 1986), the molecular events leading to the disruption of normal cardiac and craniofacial development have not been elucidated. At the genetic level, several possibilities are suggested.…”

“…U70231. ] DiGeorge syndrome (DGS) is a developmental field defect of the third and fourth branchial arches (Kirby and Bockman 1984;Lammer and Opitz 1986). The resulting phenotypes in the neonate include hypoplasia of the parathyroid gland and thymus, abnormalities of the cardiac outflow tract, and mild craniofacial dysmorphia (Conley et al 1979).…”

Temporal–spatial ablation of neural crest in the mouse results in cardiovascular defects

“…This ablation results in a very characteristic phenotype, which includes OFT defects and aortic arch patterning abnormalities, as well as abnormalities of the development of the thymus, parathyroid, and thyroid glands (Kirby, 1999;Hutson, 2003). Similar sets of abnormalities are seen in some human patients born with congenital heart disease, which led to the hypothesis that alter-ations in the biology of the neural crest were responsible for these defects in humans (Kirby and Bockman, 1984;Van Mierop and Kutsche, 1986).…”

The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome

“…Chrd mutant neonates display phenotypes characteristic of DiGeorge syndrome: lack of thymus and parathyroid glands, lack of heart colonization by neural crest, defects in pharyngeal arches 2-6, cleft palate and abnormal placement of the external ear. Two different developmental mechanisms have been proposed as possible explanations for the pathogenesis of DiGeorge syndrome: incomplete differentiation of the pharyngeal pouches (Wendling et al, 2000) and inability of peripharyngeal neural crest cells to migrate to their target organs (Kirby and Bockman, 1984). Both processes are affected in Chrd homozygous mouse mutants.…”