Neural Crest System - Abnormalities

From Embryology
Embryology - 27 Feb 2017    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Introduction

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.


Neural Crest Links: Introduction | Lecture - Early Neural | Lecture - Neural Crest Development | Schwann | Adrenal Gland | Melanocyte | Peripheral Nervous System | Enteric Nervous System | Cornea | Cranial Nerves | Cardiac | Nicole Le Douarin | Neural Crest Movies | Abnormalities | Category:Neural Crest

Some Recent Findings

  • Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans [1] "Hirschsprung (HSCR) disease is a complex genetic disorder attributed to a failure of the enteric neural crest cells (ENCCs) to form ganglia in the hindgut. Hedgehog and Notch are implicated in mediating proliferation and differentiation of ENCCs. Nevertheless, how these signaling molecules may interact to mediate gut colonization by ENCCs and contribute to a primary etiology for HSCR are not known. Here, we report our pathway-based epistasis analysis of data generated by a genome-wide association study on HSCR disease, which indicates that specific genotype constellations of Patched (PTCH1) (which encodes a receptor for Hedgehog) and delta-like 3 (DLL3) (which encodes a receptor for Notch) SNPs confer higher risk to HSCR. Importantly, deletion of Ptch1 in mouse ENCCs induced robust Dll1 expression and activation of the Notch pathway, leading to premature gliogenesis and reduction of ENCC progenitors in mutant bowels. Dll1 integrated Hedgehog and Notch pathways to coordinate neuronal and glial cell differentiation during enteric nervous system development. In addition, Hedgehog-mediated gliogenesis was found to be highly conserved, such that Hedgehog was consistently able to promote gliogenesis of human neural crest-related precursors. Collectively, we defined PTCH1 and DLL3 as HSCR susceptibility genes and suggest that Hedgehog/Notch-induced premature gliogenesis may represent a new disease mechanism for HSCR."
  • An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation.[2]
  • The developmental biology of melanocytes and its application to understanding human congenital disorders of pigmentation.[3]
More recent papers
Mark Hill.jpg
PubMed logo.gif

This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Neural Crest Abnormalities


Kenyo Takara, Naoki Maruo, Kyoko Oka, Chiaki Kaji, Yuji Hatakeyama, Naruhiko Sawa, Yukinari Kato, Junro Yamashita, Hiroshi Kojima, Yoshihiko Sawa Morphological study of tooth development in podoplanin-deficient mice. PLoS ONE: 2017, 12(2);e0171912 PubMed 28222099

Shi-Yu Yang, Michelle Beavan, Kai-Yin Chau, Jan-Willem Taanman, Anthony H V Schapira A Human Neural Crest Stem Cell-Derived Dopaminergic Neuronal Model Recapitulates Biochemical Abnormalities in GBA1 Mutation Carriers. Stem Cell Reports: 2017; PubMed 28216145

Linlea Armstrong, Maja Tarailo-Graovac, Graham Sinclair, Kimberly I Seath, Wyeth W Wasserman, Colin J Ross, Clara D M van Karnebeek A girl with developmental delay, ataxia, cranial nerve palsies, severe respiratory problems in infancy-Expanding NDST1 syndrome. Am. J. Med. Genet. A: 2017, 173(3);712-715 PubMed 28211985

C Seinturier, S Blaise, F Thony, J L Magne, G Pernod A femoral common vein aneurysm in a patient with neurofibromatosis syndrome type 1. Ann Vasc Surg: 2017; PubMed 28163183

A Hudson, M Macdonald, J N Friedman, K Blake CHARGE syndrome gastrointestinal involvement: from mouth to anus. Clin. Genet.: 2016; PubMed 28155231

Neuroblastoma

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%).

Neuroblastoma (Image: NZ Crown copyright)


Changes in Chilhood Survival Rates - Neuroblastoma

Cancer Infant number (percentage)
acute leukemia 21 infants (25.6%; acute myeloid leukemia in 12, and acute lymphoblastic leukemia in 9)
retinoblastoma 14 (17.1%)
neuroblastoma 12 (14.6%)
brain tumor 9 (11.0%)
germ cell tumor 8 (9.8%)
hepatoblastoma 5 (6.1%)
soft tissue sarcoma 5 (rhabdomyosarcoma 1, fibrosarcoma 3, other sarcoma 1)

Childhood Cancer Survival Rates table modified from: Childhood Cancer Survivor Study


See data from[4] and another Italian study[5] 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."

Database Search: OMIM- Neuroblastoma (2006 - 242 search results)

Links: OMIM - Neuroblastoma

DiGeorge syndrome

DiGeorge chromosome 22

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.

Search PubMed: Digeorge Syndrome | Takao syndrome

Neurofibromatosis Type 1 (NF1)

  • Neurofibromatosis Type 1 (von Recklinghausen) occurs in 1 in 3,000 to 4,000 people with characteristic skin blemishes forming in early childhood.[6]
  • 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.
  • 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)

Links: OMIM - Neurofibromatosis Type 1 | Genetics Home Reference - Neurofibromatosis Type 1 | Nemours Foundation - Neurofibromatosis | Neurofibromatosis, Inc. (USA) | Atlas of Genetics and Cytogenetics in Oncology- Neurofibroma

Intestinal Aganglionosis

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, Hirschsprung's Disease or Megacolon
  • lack of enteric nervous system (neural ganglia) in the intestinal tract responsible for gastric motility (peristalsis).
  • severity is dependent upon the amount of the GIT that lacks intrinsic ganglia, due to developmental lack of neural crest migration into those segments.
  • 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.


Megacolon surgery.gif Megacolon stoma.gif
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).[7] Recent CCHS research has also identified Paired-like Homeobox 2B (PHOX2B) gene mutations associated with this disorder.

OMIM: Hirschsprung's Disease | Congenital failure of autonomic control | PHOX2B)

Search PubMed: hirschprung's+disease

Links:NIH - NIDDK - Hirschsprungs | MedlinePlus - Hirschsprung's disease

Tetralogy of Fallot

Cardiac abnormality possibly stemming from abnormal neural crest migration. Named after Etienne-Louis Arthur Fallot (1888) who described it as "la maladie blue".

Links: Cardiovascular System Development | Cardiac Tutorial | Lecture - Heart | Cardiovascular System - Abnormalities

Treacher Collins syndrome

(TCS) A genetic developmental abnormality results from autosomal dominant mutations of the gene TCOF1 encoding the protein Treacle, identified in 2006. The syndrome is characterized by hypoplasia of the facial bones, cleft palate, and middle and external ear defects. These defects may relate to the effects on neural crest migration.

Links: Neural Crest Development | OMIM - TCOF1 | PMID: 8563749)

Melanoma

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.

Links: Medline Plus - Melanoma | Cancer Council Australia - Skin cancer in Australia | American Academy of Dermatology - Melanoma: What It Looks Like | New Zealand Dermatological Society - Melanoma

Self Assessment Questions

OMIM Database

Online Mendelian Inheritence in Man Database. OMIM

Internet Search OMIM database with the keyword "neural crest" or the above abnormality names.

OMIM Sample Entries

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 SYNDROME600501 ABCD SYNDROME*256700 NEUROBLASTOMA#142623 HIRSCHSPRUNG DISEASE#162300 MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B#130650 BECKWITH-WIEDEMANN SYNDROME; BWS164210 OCULOAURICULOVERTEBRAL DYSPLASIA#171300 PHEOCHROMOCYTOMA#176270 PRADER-WILLI SYNDROME; PWS#193510 WAARDENBURG SYNDROME, TYPE IIA; WS2A214800 CHOANAL ATRESIA, POSTERIOR; PCA*600594 DIGEORGE CRITICAL REGION GENE 2249400 MELANOSIS, NEUROCUTANEOUS*155735 MELANOMA ADHESION MOLECULE; MCAM217100 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 GENE603807 PETERS ANOMALY WITH CATARACT

References

  1. Elly Sau-Wai Ngan, Maria-Mercè Garcia-Barceló, Benjamin Hon-Kei Yip, Hiu-Ching Poon, Sin-Ting Lau, Carmen Ka-Man Kwok, Eric Sat, Mai-Har Sham, Kenneth Kak-Yuen Wong, Brandon J Wainwright, Stacey S Cherny, Chi-Chung Hui, Pak Chung Sham, Vincent Chi-Hang Lui, Paul Kwong-Hang Tam Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans. J. Clin. Invest.: 2011, 121(9);3467-78 PubMed 21841314
  2. Frances A High, Maozhen Zhang, Aaron Proweller, Lili Tu, Michael S Parmacek, Warren S Pear, Jonathan A Epstein An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J. Clin. Invest.: 2007, 117(2);353-63 PubMed 17273555
  3. Thomas J Hornyak The developmental biology of melanocytes and its application to understanding human congenital disorders of pigmentation. Adv Dermatol: 2006, 22;201-18 PubMed 17249303
  4. Elisa Dama, Guido Pastore, Maria Luisa Mosso, Milena Maria Maule, Luisa Zuccolo, Corrado Magnani, Franco Merletti Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy). Eur. J. Pediatr.: 2006, 165(4);240-9 PubMed 16411094
  5. Chao-Ping Yang, Iou-Jih Hung, Tang-Her Jaing, Lee-Yung Shih, Wan-Hui Chang Cancer in infants: a review of 82 cases. Pediatr Hematol Oncol: 2005, 22(6);463-81 PubMed 16169813
  6. Sofie De Schepper, Joachim Boucneau, Jo Lambert, Ludwine Messiaen, Jean-Marie Naeyaert Pigment cell-related manifestations in neurofibromatosis type 1: an overview. Pigment Cell Res.: 2005, 18(1);13-24 PubMed 15649148
  7. G D Croaker, E Shi, E Simpson, T Cartmill, D T Cass Congenital central hypoventilation syndrome and Hirschsprung's disease. Arch. Dis. Child.: 1998, 78(4);316-22 PubMed 9623393

Reviews

Dwight R Cordero, Samantha Brugmann, Yvonne Chu, Ruchi Bajpai, Maryam Jame, Jill A Helms Cranial neural crest cells on the move: their roles in craniofacial development. Am. J. Med. Genet. A: 2011, 155A(2);270-9 PubMed 21271641

Yifei Liu, Andrew Xiao Epigenetic regulation in neural crest development. Birth Defects Res. Part A Clin. Mol. Teratol.: 2011, 91(8);788-96 PubMed 21618405

Paul A Trainor Craniofacial birth defects: The role of neural crest cells in the etiology and pathogenesis of Treacher Collins syndrome and the potential for prevention. Am. J. Med. Genet. A: 2010, 152A(12);2984-94 PubMed 20734335

Sunghoon Kim, Dai H Chung Pediatric solid malignancies: neuroblastoma and Wilms' tumor. Surg. Clin. North Am.: 2006, 86(2);469-87, xi PubMed 16580935

Chao-Ping Yang, Iou-Jih Hung, Tang-Her Jaing, Lee-Yung Shih, Wan-Hui Chang Cancer in infants: a review of 82 cases. Pediatr Hematol Oncol: 2005, 22(6);463-81 PubMed 16169813

G D Croaker, E Shi, E Simpson, T Cartmill, D T Cass Congenital central hypoventilation syndrome and Hirschsprung's disease. Arch. Dis. Child.: 1998, 78(4);316-22 PubMed 9623393


Articles

Raquel M Fernández, Marta Bleda, Berta Luzón-Toro, Luz García-Alonso, Stacey Arnold, Yunia Sribudiani, Claude Besmond, Francesca Lantieri, Betty Doan, Isabella Ceccherini, Stanislas Lyonnet, Robert Mw Hofstra, Aravinda Chakravarti, Guillermo Antiñolo, Joaquín Dopazo, Salud Borrego Pathways systematically associated to Hirschsprung's disease. Orphanet J Rare Dis: 2013, 8;187 PubMed 24289864

Elisa Dama, Guido Pastore, Maria Luisa Mosso, Milena Maria Maule, Luisa Zuccolo, Corrado Magnani, Franco Merletti Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy). Eur. J. Pediatr.: 2006, 165(4);240-9 PubMed 16411094

Ramesh Bajaj, Janine Smith, Delphine Trochet, John Pitkin, Robert Ouvrier, Nicole Graf, David Sillence, Martin Kluckow Congenital central hypoventilation syndrome and Hirschsprung's disease in an extremely preterm infant. Pediatrics: 2005, 115(6);e737-8 PubMed 15930201


Search PubMed

Search April 2010 "Neural Crest Development" - All (4354) Review (843) Free Full Text (1621)

Search Pubmed: neural crest abnormalities | neuroblastoma | Neurofibromatosis type 1

Additional Images

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

  • Children's Neuroblastoma Cancer Foundation CNCF
  • Childhood Cancer Survivor Study CCSS


Glossary Links

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols

Cite this page: Hill, M.A. 2017 Embryology Neural Crest System - Abnormalities. Retrieved February 27, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_Crest_System_-_Abnormalities

What Links Here?
© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G