Neural Crest - Melanocyte Development

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Introduction

Mouse melanoblast distribution (E12.5 - E16.5)[1]

Melanocytes provide the pigment melanin to keratinocytes in the skin epithelium. These cells are neural crest in origin and recent research suggests that skin melaocytes are derived from the same population that Schwann cells are derived. Schwann cells wrap around nerve axon processes outside of the central nervous system. These cells in development originate from neural crest cells migrating out along the developing nerve fibers and these cells differentiate to form myelin sheaths that surround the mature nerve. The cells are named after their original discoverer a German physiologist Theodor Schwann (1810 - 1882).

In mammals, these pigmented cells can also be found in other tissues such as the: eyes, ears, heart, and central nervous system meninges. Melanocyte cells are a key topic in medical research as they are the cell transformed in melanoma.

See Integumentary System Development


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

  • The exon junction complex (EJC) component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.[2] "Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis."
  • Generation of human melanocytes from induced pluripotent stem cells [3] "We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines were subsequently used to form embryoid bodies (EBs) and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes"
  • Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin[4]"Current opinion holds that pigment cells, melanocytes, are derived from neural crest cells produced at the dorsal neural tube and that migrate under the epidermis to populate all parts of the skin. Here, we identify growing nerves projecting throughout the body as a stem/progenitor niche containing Schwann cell precursors (SCPs) from which large numbers of skin melanocytes originate. SCPs arise as a result of lack of neuronal specification by Hmx1 homeobox gene function in the neural crest ventral migratory pathway. Schwann cell and melanocyte development share signaling molecules with both the glial and melanocyte cell fates intimately linked to nerve contact and regulated in an opposing manner by Neuregulin and soluble signals including insulin-like growth factor and platelet-derived growth factor. These results reveal SCPs as a cellular origin of melanocytes, and have broad implications on the molecular mechanisms regulating skin pigmentation during development, in health and pigmentation disorders."


Melanocyte development cartoon.jpg

Overview of Melanocyte Development in Mammals and Zebrafish[5]

Skin Pigmentation

Ephilis (freckle)

(pl., ephilides; freckle) Clinical term describing a "freckle", that is a small brown or tan mark on the skin. These inherited features result from a copy of variant Melanocortin 1 Receptor (MC1R) gene and are common on fair skinned Celtic children. Melanocytes produce locally more melanin, this can also increase following exposure to ultraviolet radiation in sunlight.

Links: OMIM MC1R

Cafe-au-lait spots

(French, cafe-au-lait = coffee with milk; café-au-lait macule; birthmark) describes the characteristic colour of the hyperpigmented skin patch. The common name (birthmark) reflects the presence at birth (congenital) or appearing in early infancy. The pigment is produced locally by melanocytes, that produce all skin pigmentation.

Appear commonly as a solitary feature, multiple café-au-lait macules are associated with various genetic syndromes including Neurofibromatosis type 1 and 2.

Links: OMIM - NF1

Mouse Melanocytes

Developing mouse ((bt9J/bt9J) melanoblast distribution in whole mount and trunk detail (green - β-galactosidase stained).[1]

Mouse Melanoblast Migration

Melanoblast migration.png
Mouse-melanoblast migration icon.jpg
 ‎‎Mouse Melanoblast
Page | Play

See also Modeling melanoblast development [6]

Links: Neural Crest Development


Zebrafish Melanocytes

Zebrafish melanocyte development model.jpg

Erbb3b gene is required to establish melanocyte stem cells in the embryo that are responsible for regenerating melanocytes after melanocytes are ablated in the larval zebrafish. Because this adult stem cell is not required for the development of embryonic melanocytes, we conclude that adult melanocyte stem cells develop in parallel to the embryonic tissues that they regulate.[7]


References

  1. 1.0 1.1 Debra L Silver, Ling Hou, Robert Somerville, Mary E Young, Suneel S Apte, William J Pavan The secreted metalloprotease ADAMTS20 is required for melanoblast survival. PLoS Genet.: 2008, 4(2);e1000003 PubMed 18454205 | PLoS Genet.
  2. Debra L Silver, Karen E Leeds, Hun-Way Hwang, Emily E Miller, William J Pavan The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes. Dev. Biol.: 2013, 375(2);172-81 PubMed 23333945
  3. Shigeki Ohta, Yoichi Imaizumi, Yohei Okada, Wado Akamatsu, Reiko Kuwahara, Manabu Ohyama, Masayuki Amagai, Yumi Matsuzaki, Shinya Yamanaka, Hideyuki Okano, Yutaka Kawakami Generation of human melanocytes from induced pluripotent stem cells. PLoS ONE: 2011, 6(1);e16182 PubMed 21249204 | PMC3020956 | PLoS One
  4. Igor Adameyko, Francois Lallemend, Jorge B Aquino, Jorge A Pereira, Piotr Topilko, Thomas Müller, Nicolas Fritz, Anna Beljajeva, Makoto Mochii, Isabel Liste, Dmitry Usoskin, Ueli Suter, Carmen Birchmeier, Patrik Ernfors Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell: 2009, 139(2);366-79 PubMed 19837037
  5. Richard L Mort, Ian J Jackson, E Elizabeth Patton The melanocyte lineage in development and disease. Development: 2015, 142(4);620-632 PubMed 25670789 | Development
  6. Lionel Larue, Florian de Vuyst, Véronique Delmas Modeling melanoblast development. Cell. Mol. Life Sci.: 2013, 70(6);1067-79 PubMed 22915137
  7. Keith A Hultman, Erine H Budi, Daniel C Teasley, Andrew Y Gottlieb, David M Parichy, Stephen L Johnson Defects in ErbB-dependent establishment of adult melanocyte stem cells reveal independent origins for embryonic and regeneration melanocytes. PLoS Genet.: 2009, 5(7);e1000544 PubMed 19578401 | PMC2699538 | PLoS Genet.

Reviews

Lukas Sommer Generation of melanocytes from neural crest cells. Pigment Cell Melanoma Res: 2011, 24(3);411-21 PubMed 21310010

Melissa L Harris, Laura L Baxter, Stacie K Loftus, William J Pavan Sox proteins in melanocyte development and melanoma. Pigment Cell Melanoma Res: 2010, 23(4);496-513 PubMed 20444197

Patrik Ernfors Cellular origin and developmental mechanisms during the formation of skin melanocytes. Exp. Cell Res.: 2010, 316(8);1397-407 PubMed 20211169

Cynthia D Cooper, David W Raible Mechanisms for reaching the differentiated state: Insights from neural crest-derived melanocytes. Semin. Cell Dev. Biol.: 2009, 20(1);105-10 PubMed 18935965


Articles

Yulin Li, Xuping Zhu, Liu Yang, Junying Li, Zhengxing Lian, Ning Li, Xuemei Deng Expression and network analysis of genes related to melanocyte development in the Silky Fowl and White Leghorn embryos. Mol. Biol. Rep.: 2011, 38(2);1433-41 PubMed 20848220

C Claus Stolt, Petra Lommes, Simone Hillgärtner, Michael Wegner The transcription factor Sox5 modulates Sox10 function during melanocyte development. Nucleic Acids Res.: 2008, 36(17);5427-40 PubMed 18703590

Carmit Levy, Mehdi Khaled, David E Fisher MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med: 2006, 12(9);406-14 PubMed 16899407


Search PubMed

Search Dec 2010 "Melanocyte Development" All (2294) Review (443) Free Full Text (704)

Search Pubmed: Melanocyte Development

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Cite this page: Hill, M.A. 2017 Embryology Neural Crest - Melanocyte Development. Retrieved March 23, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_Crest_-_Melanocyte_Development

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