While the cells originate from the ectoderm layer, unlike the neural tube which "pinches off" from the surface ectoderm, the neural crest cells head off on migrations throughout the embryo forming a diverse range of cell types and contributions to different tissues.
This behaviour also means that failure of correct migration or differentiation can lead to a number of different abnormalities.
High FA, Zhang M, Proweller A, Tu L, Parmacek MS, Pear WS, Epstein JA. An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007 Feb;117(2):353-63.
Hornyak TJ. The developmental biology of melanocytes and its application to understanding human congenital disorders of pigmentation. Adv Dermatol. 2006;22:201-18.
Neuroblastoma (Image: NZ Crown copyright)
Changes in Chilhood Survival Rates - Neuroblastoma
Childhood Cancer Survival Rates (table modified from: Childhood Cancer Survivor Study)
A smaller recent infant cancer study (Tiwan, Medical Center Cancer Registry, 1995 - 2001) of 82 infants (40 males and 42 females, 12 neonates) showed neuroblastoma as the third most common infant cancer (12 infants 14.6%).
Infant number (percentage)
21 infants (25.6%; acute myeloid leukemia in 12, and acute lymphoblastic leukemia in 9)
germ cell tumor
soft tissue sarcoma
5 (rhabdomyosarcoma 1, fibrosarcoma 3, other sarcoma 1)
(Data from: Yang CP, Hung IJ, Jaing TH, Shih LY, Chang WH. Cancer in infants: a review of 82 cases. Pediatr Hematol Oncol. 2005 Sep;22(6):463-81.)
Another Italian study showed: "Age of less than 1 year at time of diagnosis was a favorable prognostic factor for neuroblastoma and ganglioneuroblastoma. The extent of disease at diagnosis was related to prognosis for neuroblastoma and ganglioneuroblastoma and other selected solid tumors."
(From: Yang CP, Hung IJ, Jaing TH, Shih LY, Chang WH. Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy). Eur J Pediatr. 2006 Apr;165(4):240-9.
Database Search: OMIM- Neuroblastoma (2006 - 242 search results)
Links: OMIM - Neuroblastoma
DiGeorge syndrome is the most frequent microdeletion syndrome in humans caused by a hemizygous deletion (1.5 to 3.0-Mb) of chromosome 22q11.2.
Velo-cardio-facial syndrome, Hypoplasia of thymus and parathyroids, third and fourth pharyngeal pouch syndrome.
Abnormalities: cardiovascular, thymic and parathyroid, craniofacial anomalies, renal anomalies, hypocalcemia and immunodeficiency.
Links: OMIM - Digeorge Syndrome |
References: Wurdak H, Ittner LM, Sommer L. DiGeorge syndrome and pharyngeal apparatus development. Bioessays. 2006 Nov;28(11):1078-86.
Neurofibromatosis Type 1 occurs in 1 in 3,000 to 4,000 people with characteristic skin blemishes forming in early childhood.
Multiple café-au-lait spots (flat skin patches darker than the surrounding area) appear in early childhood which increase in both size and number with age. In addition to these skin changes, tumors can develop along nerves in the skin, brain, and other parts of the body. In the iris of the eye, Lisch nodules (benign growths) also appear.
(French, café-au-lait = coffee with milk)
References: De Schepper S, Boucneau J, Lambert J, Messiaen L, Naeyaert JM. Pigment cell-related manifestations in neurofibromatosis type 1: an overview. Pigment Cell Res. 2005 Feb;18(1):13-24. Review.
Intestinal Aganglionosis, also known as Hirschsprung's Disease or Megacolon, is a lack of enteric nervous system (neural ganglia) in the intestinal tract responsible for gastric motility (peristalsis).
In general, its severity is dependent upon the amount of the GIT that lacks intrinsic ganglia, due to developmental lack of neural crest migration into those segments. (More? Gastrointestinal Tract Abnormalities - Intestinal Aganglionosis)
Short section of the colon without smooth muscle neural ganglia
Longer section without ganglia
The first indication in newborns is an absence of the first bowel movement, other symptoms include throwing up and intestinal infections. Clinically this is detected by one or more tests (barium enema and x ray, manometry or biopsy) and can currently only be treated by surgery. A temoporary ostomy (Colostomy or Ileostomy) with a stoma is carried out prior to a more permanent pull-through surgery.
Congenital failure of autonomic control describes the occasional association with congenital central hypoventilation syndrome (CCHS, Ondine's curse or Haddad Syndrome) perhaps correlating with a failure of neural crest associated with the respiratory system. This condition is a decrease in respiration (hypoventilation) usually during sleep and an insensitivity to stimuli which should increase respiration (hypercarbia and hypoxia). (More? Croaker etal., 1998) Recent CCHS research has also identified Paired-like Homeobox 2B (PHOX2B) gene mutations associated with this disorder.
Search PubMed: hirschprung's+disease
In Australia each year 8,800 people are diagnosed with melanoma, and almost 1000 people die (Data, Cancer Council Australia).
Two different findings on the reprogramming of melanoma cells, which have a neural crest origin, when transplanted between species into embryos.
Kulesa PM, Kasemeier-Kulesa JC, Teddy JM, Margaryan NV, Seftor EA, Seftor RE, Hendrix MJ. Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment. Proc Natl Acad Sci U S A. 2006 Feb 27; [Epub ahead of print]
Lee LM, Seftor EA, Bonde G, Cornell RA, Hendrix MJ. The fate of human malignant melanoma cells transplanted into zebrafish embryos: assessment of migration and cell division in the absence of tumor formation. Dev Dyn. 2005 Aug;233(4):1560-70.
Online Mendelian Inheritence in Man Database. OMIM
Internet Search OMIM database with the keyword "neural crest" or the above abnormality names.
Neural Crest disease entries from 74 entries found (1999 search), using "neural crest"
*193500 WAARDENBURG SYNDROME, TYPE I; WS1
*162200 NEUROFIBROMATOSIS, TYPE I; NF1
*188400 DIGEORGE SYNDROME; DGS
#171400 MULTIPLE ENDOCRINE NEOPLASIA, TYPE II; MEN2
#277580 WAARDENBURG-SHAH SYNDROME
600501 ABCD SYNDROME
#142623 HIRSCHSPRUNG DISEASE
#162300 MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B
#130650 BECKWITH-WIEDEMANN SYNDROME; BWS
164210 OCULOAURICULOVERTEBRAL DYSPLASIA
#176270 PRADER-WILLI SYNDROME; PWS
#193510 WAARDENBURG SYNDROME, TYPE IIA; WS2A
214800 CHOANAL ATRESIA, POSTERIOR; PCA
*600594 DIGEORGE CRITICAL REGION GENE 2
249400 MELANOSIS, NEUROCUTANEOUS
*155735 MELANOMA ADHESION MOLECULE; MCAM
217100 CONSTRICTING BANDS, CONGENITAL
#146150 HYPOMELANOSIS OF ITO; HMI
#137600 IRIDOGONIODYSGENESIS, TYPE 2; IRID2
#188550 THYROID CARCINOMA, PAPILLARY
*601499 RIEGER SYNDROME, TYPE 2; RIEG2
#601631 IRIDOGONIODYSGENESIS, TYPE 1; IRID1
*601654 EYES ABSENT 2; EYA2
#118200 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1B; CMT1B
#106200 ANIRIDIA; AN1
*602942 NEUROBLASTOMA STAGE 4S GENE
603807 PETERS ANOMALY WITH CATARACT
Kim S, Chung DH. Pediatric solid malignancies: neuroblastoma and Wilms' tumor. Surg Clin North Am. 2006 Apr;86(2):469-87, xi.
Yang CP, Hung IJ, Jaing TH, Shih LY, Chang WH. Cancer in infants: a review of 82 cases. Pediatr Hematol Oncol. 2005 Sep;22(6):463-81.
Croaker GD, Shi E, Simpson E, Cartmill T, Cass DT. Congenital central hypoventilation syndrome and Hirschsprung's disease. Arch Dis Child. 1998 Apr;78(4):316-22.
Yang CP, Hung IJ, Jaing TH, Shih LY, Chang WH. Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy). Eur J Pediatr. 2006 Apr;165(4):240-9.
Bajaj R, Smith J, Trochet D, Pitkin J, Ouvrier R, Graf N, Sillence D, Kluckow M. Congenital central hypoventilation syndrome and Hirschsprung's disease in an extremely preterm infant. Pediatrics. 2005 Jun;115(6):e737-8.
Search May 2006 "neuroblastoma" 23,482 reference articles of which 1,707 were reviews.