TY - JOUR

T1 - mc1r Pathway regulation of zebrafish melanosome dispersion

AU - Richardson, Jennifer

AU - Lundegaard, Pia Rengtved

AU - Reynolds, Natalie L

AU - Dorin, Julia R

AU - Porteous, David J

AU - Jackson, Ian J

AU - Patton, E Elizabeth

PY - 2008/12

Y1 - 2008/12

N2 - Zebrafish rapidly alter their pigmentation in response to environmental changes. For black melanocytes, this change is due to aggregation or dispersion of melanin in the cell. Dispersion and aggregation are controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, which increase upon stimulation by alpha melanocyte-stimulating hormone (alpha-MSH) or reduce with melanin-concentrating hormone (MCH). In mammals and birds, the melanocortin-1-receptor (MC1R) responds to MSH, and stimulates the synthesis of black eumelanin. While MSH-cAMP signaling stimulates melanogenesis in mammals, and melanosome dispersal in cold-blood vertebrates, the pathway components are highly conserved. However, it has only been assumed that mc1r mediates melanosome dispersal in fish. Here, using morpholino oligonucleotides designed to knockdown mc1r expression, we find that mc1r morphants are unable to disperse melanosomes when grown in dark conditions. We also use chemical modifiers of the cAMP pathway, and find an unexpected response to the specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, in melanosome dispersal. When treated with the drug, melanosomes fail to fully disperse in dark conditions, despite presumed increased levels of cAMP, and in contrast to the effects of the nonselective PDE inhibitor, 3-isobutyl-1-methylxanthine. In conclusion, we demonstrate a direct role for mc1r in zebrafish melanosome dispersal in response to background, and use chemical modification of this pathway to uncover a possible new layer of regulation in melanosome dispersal in zebrafish.

AB - Zebrafish rapidly alter their pigmentation in response to environmental changes. For black melanocytes, this change is due to aggregation or dispersion of melanin in the cell. Dispersion and aggregation are controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, which increase upon stimulation by alpha melanocyte-stimulating hormone (alpha-MSH) or reduce with melanin-concentrating hormone (MCH). In mammals and birds, the melanocortin-1-receptor (MC1R) responds to MSH, and stimulates the synthesis of black eumelanin. While MSH-cAMP signaling stimulates melanogenesis in mammals, and melanosome dispersal in cold-blood vertebrates, the pathway components are highly conserved. However, it has only been assumed that mc1r mediates melanosome dispersal in fish. Here, using morpholino oligonucleotides designed to knockdown mc1r expression, we find that mc1r morphants are unable to disperse melanosomes when grown in dark conditions. We also use chemical modifiers of the cAMP pathway, and find an unexpected response to the specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, in melanosome dispersal. When treated with the drug, melanosomes fail to fully disperse in dark conditions, despite presumed increased levels of cAMP, and in contrast to the effects of the nonselective PDE inhibitor, 3-isobutyl-1-methylxanthine. In conclusion, we demonstrate a direct role for mc1r in zebrafish melanosome dispersal in response to background, and use chemical modification of this pathway to uncover a possible new layer of regulation in melanosome dispersal in zebrafish.

KW - 1-Methyl-3-isobutylxanthine

KW - Animals

KW - Gene Expression Regulation, Developmental

KW - Gene Silencing

KW - Melanins

KW - Melanocytes

KW - Melanosomes

KW - Receptor, Melanocortin, Type 2

KW - Rolipram

KW - Zebrafish

U2 - 10.1089/zeb.2008.0541

DO - 10.1089/zeb.2008.0541

M3 - Journal article

C2 - 19133827

VL - 5

SP - 289

EP - 295

JO - Zebrafish

JF - Zebrafish

SN - 1545-8547

IS - 4

ER -