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The melanocyte lineage in development and disease.

Mort RL, Jackson IJ, Patton EE - Development (2015)

Bottom Line: Melanocyte development provides an excellent model for studying more complex developmental processes.In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches.This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Genetics Unit and.

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An overview of melanocyte development. (A) In mammals, melanoblasts are specified from neural crest cells (NCCs) via a SOX10-positive melanoblast/glial bipotent progenitor. SOX10 expression remains switched on in both of these lineages. Melanoblasts subsequently are specified and acquire MITF, DCT and KIT expression. After colonising the developing embryonic hair follicles, some melanoblasts differentiate into melanocytes and produce the pigment (melanin) that colours the first hair cycle. A subset of melanoblasts dedifferentiate (losing MITF and KIT expression but not DCT) to form melanocyte stem cells in the hair follicle bulge that replenish the differentiated melanocytes via a rapidly proliferating transit-amplifying cell in the subsequent hair cycles. The image on the far right is of a transgenic mouse embryo expressing lacZ under control of the melanoblast promoter Dct. X-Gal staining reveals blue-stained melanoblasts, in particular those migrating from the cervical neural crest and in the head. Also stained are the telencephalon, the dorsal root ganglia (DRG) and the retinal pigmented epithelium of the eye. (B) In zebrafish, there are distinct embryonic and adult pigmentation patterns, as illustrated in the images on the far right. The melanoblasts that form both these patterns originate from a SOX10-positive neural crest-derived progenitor. The embryonic pattern is formed by melanocytes that develop directly from this progenitor via an MITF+ melanoblast. The melanoblasts that form the adult pattern are derived from a melanocyte stem cell population that resides at the dorsal route ganglia (DRG) and is specified by an ERB- and KIT-dependent pathway in the embryo.
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DEV106567F1: An overview of melanocyte development. (A) In mammals, melanoblasts are specified from neural crest cells (NCCs) via a SOX10-positive melanoblast/glial bipotent progenitor. SOX10 expression remains switched on in both of these lineages. Melanoblasts subsequently are specified and acquire MITF, DCT and KIT expression. After colonising the developing embryonic hair follicles, some melanoblasts differentiate into melanocytes and produce the pigment (melanin) that colours the first hair cycle. A subset of melanoblasts dedifferentiate (losing MITF and KIT expression but not DCT) to form melanocyte stem cells in the hair follicle bulge that replenish the differentiated melanocytes via a rapidly proliferating transit-amplifying cell in the subsequent hair cycles. The image on the far right is of a transgenic mouse embryo expressing lacZ under control of the melanoblast promoter Dct. X-Gal staining reveals blue-stained melanoblasts, in particular those migrating from the cervical neural crest and in the head. Also stained are the telencephalon, the dorsal root ganglia (DRG) and the retinal pigmented epithelium of the eye. (B) In zebrafish, there are distinct embryonic and adult pigmentation patterns, as illustrated in the images on the far right. The melanoblasts that form both these patterns originate from a SOX10-positive neural crest-derived progenitor. The embryonic pattern is formed by melanocytes that develop directly from this progenitor via an MITF+ melanoblast. The melanoblasts that form the adult pattern are derived from a melanocyte stem cell population that resides at the dorsal route ganglia (DRG) and is specified by an ERB- and KIT-dependent pathway in the embryo.

Mentions: The transcription factor microphthalmia-associated transcription factor (MITF) appears to be the master regulator of melanocyte identity and is embedded within a transcriptional network (Fig. 1) that controls the development of melanocytes from the neural crest [reviewed by Baxter et al. (2010)]. Mice lacking MITF cannot form melanocytes (Steingrímsson et al., 2004). Similarly, fish lacking one of the MITF orthologues, mitfa, have no melanocytes, and ectopic expression of mitfa can produce ectopic melanocytes (Lister et al., 1999). Furthermore, the expression of MITF in Medaka embryo-derived stem cells induces differentiation into melanocytes (Béjar et al., 2003), and MITF expression in NIH3T3 cells can activate melanocyte markers (Tachibana et al., 1996). Numerous MITF transcriptional targets have been identified, and include genes encoding components of melanocyte-specific organelles (melanosomes) and the melanin synthesis pathway (see Box 1) as well as more widely expressed genes such as the survival gene Bcl2 (Cheli et al., 2010). In humans, germline mutations in MITF can lead to Waardenburg syndrome or Tietz syndrome [Online Mendelian Inheritance in Man database (OMIM) entries 193510 and 103500, respectively], which are characterised by lack of pigmentation and deafness, as melanocytes also play an important function in the ear. In addition, more subtle changes in MITF transcriptional activity regulated by IRF1 are partially responsible for the pale skin, blue eyes and freckling with brown hair seen in some Northern European populations (Praetorius et al., 2013).Fig. 1.


The melanocyte lineage in development and disease.

Mort RL, Jackson IJ, Patton EE - Development (2015)

An overview of melanocyte development. (A) In mammals, melanoblasts are specified from neural crest cells (NCCs) via a SOX10-positive melanoblast/glial bipotent progenitor. SOX10 expression remains switched on in both of these lineages. Melanoblasts subsequently are specified and acquire MITF, DCT and KIT expression. After colonising the developing embryonic hair follicles, some melanoblasts differentiate into melanocytes and produce the pigment (melanin) that colours the first hair cycle. A subset of melanoblasts dedifferentiate (losing MITF and KIT expression but not DCT) to form melanocyte stem cells in the hair follicle bulge that replenish the differentiated melanocytes via a rapidly proliferating transit-amplifying cell in the subsequent hair cycles. The image on the far right is of a transgenic mouse embryo expressing lacZ under control of the melanoblast promoter Dct. X-Gal staining reveals blue-stained melanoblasts, in particular those migrating from the cervical neural crest and in the head. Also stained are the telencephalon, the dorsal root ganglia (DRG) and the retinal pigmented epithelium of the eye. (B) In zebrafish, there are distinct embryonic and adult pigmentation patterns, as illustrated in the images on the far right. The melanoblasts that form both these patterns originate from a SOX10-positive neural crest-derived progenitor. The embryonic pattern is formed by melanocytes that develop directly from this progenitor via an MITF+ melanoblast. The melanoblasts that form the adult pattern are derived from a melanocyte stem cell population that resides at the dorsal route ganglia (DRG) and is specified by an ERB- and KIT-dependent pathway in the embryo.
© Copyright Policy - open-access
Related In: Results  -  Collection

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DEV106567F1: An overview of melanocyte development. (A) In mammals, melanoblasts are specified from neural crest cells (NCCs) via a SOX10-positive melanoblast/glial bipotent progenitor. SOX10 expression remains switched on in both of these lineages. Melanoblasts subsequently are specified and acquire MITF, DCT and KIT expression. After colonising the developing embryonic hair follicles, some melanoblasts differentiate into melanocytes and produce the pigment (melanin) that colours the first hair cycle. A subset of melanoblasts dedifferentiate (losing MITF and KIT expression but not DCT) to form melanocyte stem cells in the hair follicle bulge that replenish the differentiated melanocytes via a rapidly proliferating transit-amplifying cell in the subsequent hair cycles. The image on the far right is of a transgenic mouse embryo expressing lacZ under control of the melanoblast promoter Dct. X-Gal staining reveals blue-stained melanoblasts, in particular those migrating from the cervical neural crest and in the head. Also stained are the telencephalon, the dorsal root ganglia (DRG) and the retinal pigmented epithelium of the eye. (B) In zebrafish, there are distinct embryonic and adult pigmentation patterns, as illustrated in the images on the far right. The melanoblasts that form both these patterns originate from a SOX10-positive neural crest-derived progenitor. The embryonic pattern is formed by melanocytes that develop directly from this progenitor via an MITF+ melanoblast. The melanoblasts that form the adult pattern are derived from a melanocyte stem cell population that resides at the dorsal route ganglia (DRG) and is specified by an ERB- and KIT-dependent pathway in the embryo.
Mentions: The transcription factor microphthalmia-associated transcription factor (MITF) appears to be the master regulator of melanocyte identity and is embedded within a transcriptional network (Fig. 1) that controls the development of melanocytes from the neural crest [reviewed by Baxter et al. (2010)]. Mice lacking MITF cannot form melanocytes (Steingrímsson et al., 2004). Similarly, fish lacking one of the MITF orthologues, mitfa, have no melanocytes, and ectopic expression of mitfa can produce ectopic melanocytes (Lister et al., 1999). Furthermore, the expression of MITF in Medaka embryo-derived stem cells induces differentiation into melanocytes (Béjar et al., 2003), and MITF expression in NIH3T3 cells can activate melanocyte markers (Tachibana et al., 1996). Numerous MITF transcriptional targets have been identified, and include genes encoding components of melanocyte-specific organelles (melanosomes) and the melanin synthesis pathway (see Box 1) as well as more widely expressed genes such as the survival gene Bcl2 (Cheli et al., 2010). In humans, germline mutations in MITF can lead to Waardenburg syndrome or Tietz syndrome [Online Mendelian Inheritance in Man database (OMIM) entries 193510 and 103500, respectively], which are characterised by lack of pigmentation and deafness, as melanocytes also play an important function in the ear. In addition, more subtle changes in MITF transcriptional activity regulated by IRF1 are partially responsible for the pale skin, blue eyes and freckling with brown hair seen in some Northern European populations (Praetorius et al., 2013).Fig. 1.

Bottom Line: Melanocyte development provides an excellent model for studying more complex developmental processes.In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches.This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Genetics Unit and.

Show MeSH
Related in: MedlinePlus