2018 Group Project 3 - Revision history

Z8600021 at 02:27, 15 April 2019

2019-04-15T02:27:24Z

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	==References==		==References==
			<references/>

Z8600021: /* Introduction */

2018-10-30T06:03:41Z

Introduction

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	==Introduction==		==Introduction==
	[[File:Melanocyte1.jpg\|350px\|thumb\|''Figure 1: Diagram of an epidermal melanocyte and its structures'']]		[[File:Melanocyte1.jpg\|350px\|thumb\|''Figure 1: Diagram of an epidermal melanocyte and its structures'']]


	Melanocytes are a type of neural crest-derived cells in the body {{#pmid:20256541\|PMID20256541}}, most commonly found in the stratum basale, the bottom layer of the epidermis of the skin, eyes {{#pmid:16704452\|PMID16704452}}, and to a lesser known degree, the meninges (membrane around the brain), the heart {{#pmid: 5476812\|PMID5476812}} and the inner ear {{#pmid: 17247639\|PMID 17247639}}.		Melanocytes are a type of neural crest-derived cells in the body {{#pmid:20256541\|PMID20256541}}, most commonly found in the stratum basale, the bottom layer of the epidermis of the skin, eyes {{#pmid:16704452\|PMID16704452}}, and to a lesser known degree, the meninges (membrane around the brain), the heart {{#pmid: 5476812\|PMID5476812}} and the inner ear {{#pmid: 17247639\|PMID 17247639}}.

Z8600021: Protected "2018 Group Project 3" ([Edit=Allow only administrators] (indefinite) [Move=Allow only administrators] (indefinite))

2018-10-17T05:06:12Z

Protected "2018 Group Project 3" ([Edit=Allow only administrators] (indefinite) [Move=Allow only administrators] (indefinite))

← Older revision	Revision as of 16:06, 17 October 2018
(No difference)

Z5229549: /* Oculocutaneous Albinism */

2018-10-17T01:40:23Z

Oculocutaneous Albinism

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	====Oculocutaneous Albinism====		====Oculocutaneous Albinism====
	[[File:Oculocutaneous_albinism_eyes.jpg\|250px\|thumb\|right\|''Figure 18: OCA1A patient eyes’’]]		[[File:Oculocutaneous_albinism_eyes.jpg\|250px\|thumb\|right\|''Figure 19: OCA1A patient eyes’’]]

	Oculocutaneous albinism is a rare group of congenital hypopigmentation disorder affecting one in 17,000 people across most ethnic backgrounds. Oculocutaneous albinism (OCA) is caused by mutations to the genes required for melanin synthesis in melanocytes resulting in the lack of pigment. In OCA, this lack of pigment results in abnormal development of the eyes leading to complications with vision (photophobia, mis-routing of optic nerves, nystagmus etc.) and significantly lighter skin which exposes the skin to UV-radiation damage from the sun.		Oculocutaneous albinism is a rare group of congenital hypopigmentation disorder affecting one in 17,000 people across most ethnic backgrounds. Oculocutaneous albinism (OCA) is caused by mutations to the genes required for melanin synthesis in melanocytes resulting in the lack of pigment. In OCA, this lack of pigment results in abnormal development of the eyes leading to complications with vision (photophobia, mis-routing of optic nerves, nystagmus etc.) and significantly lighter skin which exposes the skin to UV-radiation damage from the sun.

Z5164785 at 01:00, 17 October 2018

2018-10-17T01:00:23Z

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	====Oculocutaneous Albinism====		====Oculocutaneous Albinism====
	[[File:Oculocutaneous_albinism_eyes.jpg\|250px\|thumb\|right\|''Figure 19: OCA1A patient eyes’’]]		[[File:Oculocutaneous_albinism_eyes.jpg\|250px\|thumb\|right\|''Figure 18: OCA1A patient eyes’’]]

	Oculocutaneous albinism is a rare group of congenital hypopigmentation disorder affecting one in 17,000 people across most ethnic backgrounds. Oculocutaneous albinism (OCA) is caused by mutations to the genes required for melanin synthesis in melanocytes resulting in the lack of pigment. In OCA, this lack of pigment results in abnormal development of the eyes leading to complications with vision (photophobia, mis-routing of optic nerves, nystagmus etc.) and significantly lighter skin which exposes the skin to UV-radiation damage from the sun.		Oculocutaneous albinism is a rare group of congenital hypopigmentation disorder affecting one in 17,000 people across most ethnic backgrounds. Oculocutaneous albinism (OCA) is caused by mutations to the genes required for melanin synthesis in melanocytes resulting in the lack of pigment. In OCA, this lack of pigment results in abnormal development of the eyes leading to complications with vision (photophobia, mis-routing of optic nerves, nystagmus etc.) and significantly lighter skin which exposes the skin to UV-radiation damage from the sun.

Z5164785 at 00:59, 17 October 2018

2018-10-17T00:59:58Z

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	Melanocytes can be derived from autologous iPSCs, meaning the cells come from the one person. In this case the likelihood of the melanocytes being rejected by the immune system of the person they are being implanted in, is incredibly low. A benefit of autologous iPSCs from a patient with a pigmented disorder (such as albinism), is that the pathogenesis can be studied in order to find a suitable treatment for the disease, and possibly a cure. {{#pmid:23483397\|PMID23483397}}		Melanocytes can be derived from autologous iPSCs, meaning the cells come from the one person. In this case the likelihood of the melanocytes being rejected by the immune system of the person they are being implanted in, is incredibly low. A benefit of autologous iPSCs from a patient with a pigmented disorder (such as albinism), is that the pathogenesis can be studied in order to find a suitable treatment for the disease, and possibly a cure. {{#pmid:23483397\|PMID23483397}}

	[[File:IPSC Formation.gif\|600px\|thumb\|center\|''Figure 15: Schematic of protocol for generating melanocytes from human iPSCs.'']]		[[File:IPSC Formation.gif\|600px\|thumb\|center\|''Figure 14: Schematic of protocol for generating melanocytes from human iPSCs.'']]

	===Altered Chromosome Expression of Uveal Melanoma in the Setting of Melanocytosis===		===Altered Chromosome Expression of Uveal Melanoma in the Setting of Melanocytosis===
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	====LEOPARD Syndrome====		====LEOPARD Syndrome====
	[[File:Leopard syndrome skin appearance.jpeg\|250px\|thumb\|right\|''Figure 16: Lentigine appearance on the skin of LS patients at different ages.'']]		[[File:Leopard syndrome skin appearance.jpeg\|250px\|thumb\|right\|''Figure 15: Lentigine appearance on the skin of LS patients at different ages.'']]

	LEOPARD syndrome is a '''congenital hyperpigmentation disorder''' that causes abnormalities to the appearance and functioning of the skin, heart, genitalia and inner ears. The name LEOPARD is an acronym which describes the characteristics of the condition;		LEOPARD syndrome is a '''congenital hyperpigmentation disorder''' that causes abnormalities to the appearance and functioning of the skin, heart, genitalia and inner ears. The name LEOPARD is an acronym which describes the characteristics of the condition;
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	====Melasma====		====Melasma====
	[[File:Mixed_melasma.jpg\|200px\|thumb\|right\|''Figure 17: Mixed facial melasma of a female patient.’’]]		[[File:Mixed_melasma.jpg\|200px\|thumb\|right\|''Figure 16: Mixed facial melasma of a female patient.’’]]
	Melasma is an '''acquired hyperpigmentation disorder'''. It is a pigmentary condition occurring primarily on the face, characterised by brown patches usually found in three identified patterns; centrofacial , malar and mandibular. The most common pattern is centrofacial where pigmentation occurs on the forehead, nose, cheeks, chin and the upper lip. Malar pattern refers to the presence of melasma of the malar cheeks (cheek bones) on the face whilst the mandibular pattern features melasma on the mandible (jawline) and chin. Melasma occurring outside of the face in regions like the neck, sternum, forearms and other upper extremities is referred to as being of the extra-facial melasma pattern {{#pmid: 28726212\|PMID28726212}}.		Melasma is an '''acquired hyperpigmentation disorder'''. It is a pigmentary condition occurring primarily on the face, characterised by brown patches usually found in three identified patterns; centrofacial , malar and mandibular. The most common pattern is centrofacial where pigmentation occurs on the forehead, nose, cheeks, chin and the upper lip. Malar pattern refers to the presence of melasma of the malar cheeks (cheek bones) on the face whilst the mandibular pattern features melasma on the mandible (jawline) and chin. Melasma occurring outside of the face in regions like the neck, sternum, forearms and other upper extremities is referred to as being of the extra-facial melasma pattern {{#pmid: 28726212\|PMID28726212}}.

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	====Vitiligo====		====Vitiligo====
	[[File:Common_Vitiligo.jpg\|200px\|thumb\|right\|''Figure 18: Depigmentation seen in common Vitiligo patient.’’]]		[[File:Common_Vitiligo.jpg\|200px\|thumb\|right\|''Figure 17: Depigmentation seen in common Vitiligo patient.’’]]
	Vitiligo is an acquired hypopigmentation disorder. It occurs due to the loss of functional melanocytes resulting in chronic depigmentation of the skin in any region of the body in more than one location. It can also affect the mucous membrane inside the nose and mouth as well as the hair <ref> Filipp, F., Birlea, S., Bosenberg, M., Brash, D., Cassidy, P., Chen, S., D'Orazio, J., Fujita, M., Goh, B., Herlyn, M., Indra, A., Larue, L., Leachman, S., Le Poole, C., Liu-Smith, F., Manga, P., Montoliu, L., Norris, D., Shellman, Y., Smalley, K., Spritz, R., Sturm, R., Swetter, S., Terzian, T., Wakamatsu, K., Weber, J. and Box, N. (2018). Frontiers in pigment cell and melanoma research. Pigment Cell & Melanoma Research, 31(6), pp.728-735. </ref>.		Vitiligo is an acquired hypopigmentation disorder. It occurs due to the loss of functional melanocytes resulting in chronic depigmentation of the skin in any region of the body in more than one location. It can also affect the mucous membrane inside the nose and mouth as well as the hair <ref> Filipp, F., Birlea, S., Bosenberg, M., Brash, D., Cassidy, P., Chen, S., D'Orazio, J., Fujita, M., Goh, B., Herlyn, M., Indra, A., Larue, L., Leachman, S., Le Poole, C., Liu-Smith, F., Manga, P., Montoliu, L., Norris, D., Shellman, Y., Smalley, K., Spritz, R., Sturm, R., Swetter, S., Terzian, T., Wakamatsu, K., Weber, J. and Box, N. (2018). Frontiers in pigment cell and melanoma research. Pigment Cell & Melanoma Research, 31(6), pp.728-735. </ref>.

Z5164785: /* Genetically Engineered Mice (GEM) Models For Melanocyte Development */

2018-10-17T00:59:09Z

Genetically Engineered Mice (GEM) Models For Melanocyte Development

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	===Genetically Engineered Mice (GEM) Models For Melanocyte Development===		===Genetically Engineered Mice (GEM) Models For Melanocyte Development===
	[[File:GEM.jpeg\|200px\|thumb\|right\|''Figure 14: Overall scheme for the generation of genetically engineered mice.'']]		[[File:GEM.jpeg\|200px\|thumb\|right\|''Figure 13: Overall scheme for the generation of genetically engineered mice.'']]

	The development of melanocytes in mice and humans are very similar, except they take longer to form in humans, so mice can be used to study melanocytes as they would occur in the human body. SCF (melanocyte growth factor) is essential for the maintenance and survival of melanocytes throughout life. The receptor for SCF is c-''kit'', and if it mutates, it can lead to sterility, anaemia and pigmentation disorders. If the receptor is completely lost, it results in loss of melanocytes, primordial germ cells and haematopoietic stem cells completely. In embryonic development however, ETRB (endothelin receptor) is more important to melanocyte developed compared to c-''kit'', as it regulates the number of precursor melanoblasts that will differentiate into melanocytes.		The development of melanocytes in mice and humans are very similar, except they take longer to form in humans, so mice can be used to study melanocytes as they would occur in the human body. SCF (melanocyte growth factor) is essential for the maintenance and survival of melanocytes throughout life. The receptor for SCF is c-''kit'', and if it mutates, it can lead to sterility, anaemia and pigmentation disorders. If the receptor is completely lost, it results in loss of melanocytes, primordial germ cells and haematopoietic stem cells completely. In embryonic development however, ETRB (endothelin receptor) is more important to melanocyte developed compared to c-''kit'', as it regulates the number of precursor melanoblasts that will differentiate into melanocytes.

Z5164785: /* Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity During Melanoma Initiation */

2018-10-17T00:58:47Z

Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity During Melanoma Initiation

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	===Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity During Melanoma Initiation===		===Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity During Melanoma Initiation===
	[[File:Zebrafish_Melanoma.jpeg\|200px\|thumb\|right\|''Figure 13: Neural crest reporter expression in melanoma.'']]		[[File:Zebrafish_Melanoma.jpeg\|200px\|thumb\|right\|''Figure 12: Neural crest reporter expression in melanoma.'']]

	Melanoma is mainly driven by mutations in BRAF (particularly BRAF''V600E'') or RAS genes. Melanoma is considered to be easily treatable when it is localised and has not broken through the tissue boundary, this is known as in situ cancer. When the mutated cells begin to invade the underlying tissue, the cancer is now metastatic and cannot be treated effectively, even with newly developed kinase and immune checkpoint targeted therapies. BRAF''V600E'' gene was placed under the influence of melanocyte-specific ''mitfa''-promoter in transgenic zebrafish. When the fish were crossed with a ''p53'' mutant loss-of-function background, they developed nevi, and after a few months the nevi became invasive cancer. The ''p53'' gene is the main tumour suppressor gene that stops cell division when the cell undergoes damage. Tumours with mutations in the ''p53'' gene are more aggressive, metastatic and have a poorer patient prognosis. It was found that the fish were prone to developing one to three melanoma tumours after several months, illustrating that molecular alterations are important for tumour initiation. {{#pmid:268234333\|PMID26823433}}		Melanoma is mainly driven by mutations in BRAF (particularly BRAF''V600E'') or RAS genes. Melanoma is considered to be easily treatable when it is localised and has not broken through the tissue boundary, this is known as in situ cancer. When the mutated cells begin to invade the underlying tissue, the cancer is now metastatic and cannot be treated effectively, even with newly developed kinase and immune checkpoint targeted therapies. BRAF''V600E'' gene was placed under the influence of melanocyte-specific ''mitfa''-promoter in transgenic zebrafish. When the fish were crossed with a ''p53'' mutant loss-of-function background, they developed nevi, and after a few months the nevi became invasive cancer. The ''p53'' gene is the main tumour suppressor gene that stops cell division when the cell undergoes damage. Tumours with mutations in the ''p53'' gene are more aggressive, metastatic and have a poorer patient prognosis. It was found that the fish were prone to developing one to three melanoma tumours after several months, illustrating that molecular alterations are important for tumour initiation. {{#pmid:268234333\|PMID26823433}}

Z5164785: /* Transcription */

2018-10-17T00:58:19Z

Transcription

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	===Transcription===		===Transcription===
	Microphthalmia transcription factor (MITF) is the key regulator of melanocyte identity without which melanocytes cannot be developed from the neural crest. The activation of MITF is a crucial stage in the formation of melanocytes. MITF have specific transcriptional targets, in particular genes which encode for melanosomes and the melanin synthesis pathway. Mutations to this transcription factor can lead to medical complications such as Waardernburg syndrome which has been discussed below. Furthermore, MITF is required to regulate the melanocyte lineage and subsequent melanocyte development.		Microphthalmia transcription factor (MITF) is the key regulator of melanocyte identity without which melanocytes cannot be developed from the neural crest. The activation of MITF is a crucial stage in the formation of melanocytes. MITF have specific transcriptional targets, in particular genes which encode for melanosomes and the melanin synthesis pathway. Mutations to this transcription factor can lead to medical complications such as Waardernburg syndrome which has been discussed below. Furthermore, MITF is required to regulate the melanocyte lineage and subsequent melanocyte development. However, The over-expression of MITF during transcription has been shown to be a characteristic of melanomas.

	MITF has been shown to be influenced by the up-regulation of WNT3A which induces melanoblast expression. <ref> Mort, R., Jackson, I. and Patton, E. (2015). The melanocyte lineage in development and disease. Development, 142(4), pp.620-632. </ref>		MITF has been shown to be influenced by the up-regulation of WNT3A which induces melanoblast expression. <ref> Mort, R., Jackson, I. and Patton, E. (2015). The melanocyte lineage in development and disease. Development, 142(4), pp.620-632. </ref>

	~~The over-expression of MITF during transcription has been shown to be a characteristic of melanomas.~~

	===Signalling Molecules===		===Signalling Molecules===

Z5164785: /* Signalling Molecules */

2018-10-17T00:57:21Z

Signalling Molecules

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	===Signalling Molecules===		===Signalling Molecules===
	[[File:~~Wnt signalling in melanocyte differentiation~~.jpg\|200px\|thumb\|right\|''Figure 11: Wnt signalling in melanocyte differentiation’’]]		[[File:Wnt_signalling.jpg\|200px\|thumb\|right\|''Figure 11: Wnt signalling in melanocyte differentiation’’]]
	There are numerous signalling molecules and associated pathways involved in melanocyte development proliferation. These include MAPK-kinase signalling, α-MSH/cAMP/PKA and Endothelin/PKC (PKA protein kinase A, PKC protein kinase C). *		There are numerous signalling molecules and associated pathways involved in melanocyte development proliferation. These include MAPK-kinase signalling, α-MSH/cAMP/PKA and Endothelin/PKC (PKA protein kinase A, PKC protein kinase C). *
	*MAPK= mitogen-activated protein (MAP) kinases		*MAPK= mitogen-activated protein (MAP) kinases