Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.
OBJECTIVE
This review highlights the relevance of the neural crest (NC) as a developmental control mechanism involved in several pediatric surgical conditions and the investigative interest of following some of its known signaling pathways.


METHODS
The participation of the NC in facial clefts, ear defects, branchial fistulae and cysts, heart outflow tract and aortic arch anomalies, pigmentary disorders, abnormal enteric innervation, neural tumors, hemangiomas, and vascular anomalies is briefly reviewed. Then, the literature on clinical and experimental esophageal atresia-tracheoesophageal fistula (EA-TEF) and congenital diaphragmatic hernia (CDH) is reviewed for the presence of associated NC defects. Finally, some of the molecular signaling pathways involved in both conditions (sonic hedgehog, Hox genes, and retinoids) are summarized.


RESULTS
The association of facial, cardiovascular, thymic, parathyroid, and C-cell defects together with anomalies of extrinsic and intrinsic esophageal innervation in babies and/or animals with both EA-TEF and CDH strongly supports the hypothesis that NC is involved in the pathogenesis of these malformative clusters. On the other hand, both EA-TEF and CDH are observed in mice mutant for genes involved in the previously mentioned signaling pathways.


CONCLUSIONS
The investigation of NC-related molecular pathogenic pathways involved in malformative associations like EA-TEF and CDH that are induced by chromosomal anomalies, chemical teratogens, and engineered mutations is a promising way of clarifying why and how some pediatric surgical conditions occur. Pediatric surgeons should be actively involved in these investigations.
Tovar
Juan A
JA
Departamento de Cirugía Pediátrica, Hospital Universitario La Paz, 28046 Madrid, Spain. jatovar.hulp@salud.madrid.org
D000015:Abnormalities, Multiple / Q000196:embryology* / Q000503:physiopathology / Q000601:surgery; D001808:Blood Vessels / Q000002:abnormalities; D001934:Branchial Region / Q000002:abnormalities; D018376:Cardiovascular Abnormalities / Q000196:embryology / Q000503:physiopathology; D019070:Cell Lineage; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D017615:Enteric Nervous System / Q000002:abnormalities; D004933:Esophageal Atresia / Q000196:embryology / Q000503:physiopathology / Q000601:surgery; D005145:Face / Q000002:abnormalities; D005801:Genes, Homeobox; D053823:Hedgehog Proteins / Q000502:physiology; D006548:Hernia, Diaphragmatic / Q000196:embryology / Q000503:physiopathology / Q000601:surgery; D065630:Hernias, Diaphragmatic, Congenital; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009369:Neoplasms / Q000209:etiology; D009432:Neural Crest / Q000503:physiopathology*; D000072079:Patched Receptors; D010859:Pigmentation Disorders / Q000209:etiology; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000502:physiology; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013577:Syndrome; D014157:Transcription Factors / Q000502:physiology; D014212:Tretinoin / Q000502:physiology; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018168:Receptors, Retinoic Acid; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D014212:Tretinoin