Craniocaudal Migration/Neurocristopathy

Abstract

Craniocaudal migration theory was presented as a classical pathogenesis of Hirschsprung’s disease (HD) by Okamoto and Ueda in 1967, showing that the human myenteric plexus was formed by neuroblasts which were distributed to the alimentary tract by craniocaudal direction during the fifth to the twelfth week of gestation. Later, it had long been accepted that neural crest cells (NCCs) either enter the foregut mesenchyme proximally and migrate down its length in a rostral to caudal fashion (vagal NCCs) or they enter the gut at the distal end and migrate caudal to rostral (sacral NCCs). Recently, it has been proposed that transmesenteric NCCs constituted a large part of the hindgut enteric nervous system by taking a shortcut to the colon. The maldevelopment of vagal or transmesenteric NCCs is considered to be a pathogenesis of HD. The term “neurocristopathy” was presented for a category of neural crest maldevelopment by Bolande in 1974. HD is a simple neurocristopathy. There have been reported various simple nonneoplastic and neoplastic neurocristopathies. Complex neurocristopathies associated with HD include Waardenburg syndrome type 4 (Waardenburg-Shah syndrome), neuroblastoma, multiple endocrine neoplasia type 2, congenital central hyperventilation, and others. It is important to screen an association of nonneoplastic and neoplastic neurocristopathies in patients who have a neurocristopathy.