Wildtype, grey-morph and partial grey-morph phenotypes of southern right whales.

<p><i>Wild-type</i> adults (panel a) have black skin and often have white skin patches on their bellies. <i>Grey morphs</i> (calf in panel b) are primarily white at birth with splatterings of rounded black spots that extend dorso-laterally around their bodies (calf in panel b). Their white skin becomes light grey or brown with age (panel c). <i>Partial grey morphs</i> are primarily black with splatterings of white skin at birth (calf in panel d) which also darkens with age (adults in panels b and d).. (Photos: J. Atkinson, Ocean Alliance).</p

Light microscopy reveals reduced pigmentation and a decreased number of melanocytes in the affected skin of grey-morph SRWs.

<p>A comparison of Fontana Masson melanin staining is shown in wild type (Panels A, C, and E) versus grey-morph SRWs (Panels B, D, and F) at low-power (20X, Panels A and B), high-power (400X, Panels C and D), and extra high-power (600X, Panels E and F) magnification. Low-power magnification shows less melanin staining, particularly in the melanocytes distributed along the basal layer of the epidermal rete ridges (arrowheads, Panels A and B). Rete ridges and dermal papillae appear similar in grey-morph and wild-type whales. Dermal papillae are marked with “= >” in panels A, B and C. High-power magnification shows reduced melanin content and fewer positively-stained cells in the grey-morph skin (Panels C and D). Extra high-power magnification shows typical melanocyte dendrite morphology (arrowhead, Panels E and F) and normal melanosome transfer and capping of keratinocyte nuclei (asterisks, Panels E and F).</p

Identities and characteristics of sampled whales.

<p>Identities and characteristics of sampled whales.</p

Melanocyte counts are reduced in grey-morph relative to wild-type SRW skin.

<p>Bars represent the absolute number of melanocytes counted in grey-morph and wild-type whales. Darkly shaded bars represent the number of melanocytes in each of 5 high-powered fields and lightly shaded blue bars represent the number of melanocytes along each 0.25 mm of the basement membrane measured. Data were compared for both measurement methods using T-tests. Both tests yielded p-values smaller than 1x10^-5.</p

KIT activation & up-regulation, concomitant parallel induction of ET3, KIT⁺Melan-A^–- progenitor cells, and melanocyte regeneration in proportion to sun-exposure.

<p>(<b><i>A</i></b>), IHC of KIT and ET3 on serial sections of human skin specimen obtained from a lower extremity-amputation. Sole represents active suppression of melanogenesis (<i>a</i> and <i>d</i>), dorsum of big toe represents intermediate sun-exposure (<i>b</i> and <i>e</i>), and lateral lower leg represents heavy sun-exposure (<i>c</i> and <i>f</i>). (<b><i>B</i></b>), IHC of KIT, Melan-A, and ET3 on serial sections of human skin punch biopsy specimens obtained from sun-protected axilla (<i>g</i>, <i>i</i>, <i>k</i>) and chronic heavy sun-exposed forearm (<i>h</i>, <i>j</i>, <i>l</i>) from the same individual. Lymphocytes serve as internal negative control for KIT, ET3 and Melan-A; mast cells serve as internal positive control for KIT. Together, these images demonstrate that human skin exhibits sun-exposure-dependent up-regulation of KIT (<i>a-c</i>) and concomitant parallel sun-exposure-induced increasing induction of ET3 (<i>d-f</i>). Chronic sun-exposure induces intense dendritic pattern of KIT expression as well as a large increase in the number of KIT-expressing-cells in the basal layer (<i>h</i>) consisting of KIT⁺Melan-A⁺ mature melanocytes (<i>j</i>) and KIT⁺Melan-A^–melanocyte progenitor cells as evidenced by the difference between (<i>h</i>) and (<i>j</i>).</p

Microarray analysis comparing a highly aggressive GIST with an indolent GIST: A selective list of target genes whose expression was up- or down-regulated by KIT signaling.

<p>Microarray analysis comparing a highly aggressive GIST with an indolent GIST: A selective list of target genes whose expression was up- or down-regulated by KIT signaling.</p

Immunohistochemical studies on human colon myenteric plexus demonstrate that 48 hours fasting results in activation of SCF-KIT signaling and concomitant parallel induction of endothelin-3.

<p>Human colon specimens post 48 hours fasting demonstrate intense KIT staining in ICCs within the myenteric plexus (<i>a</i>), and intense ET3 staining within the myenteric plexus (<i>b</i>). In sharp contrast, the surrounding longitudinal and circular smooth muscle cells (SM) show negative ET3 staining.</p

Autophosphorylation, internalization, and nuclear localization of activated KIT with tyrosine phosphorylation at 568/570 (pY568/pY570KIT).

<p>(<b><i>A</i></b>), IHC of frozen sections of an aggressive GIST (<i>a-c</i>) and a normal human adult testis as external control (<i>d-f</i>) using pan-KIT antibody (<i>a</i> and <i>d</i>), pY568/pY570KIT antibody (b and <i>e</i>, red arrow indicates nuclear localization), and pY703KIT antibody (<i>c</i> and <i>f</i>) respectively. (<b><i>B</i></b>), <i>In situ</i> IHC to assess kinetics of SCF-induced nuclear translocation of pY568/pY570KIT using WM793 melanoma cells cultured in 4-well chamber tissue culture treated glass slides. Control (<i>g)</i> without SCF stimulation, after addition of SCF to culture media, the nuclear localization of pY568/pY570KIT increases progressively (<i>h-j</i>) in more than 90% of WM793 cells, reaches a plateau about 40–60 minutes (<i>i</i> and <i>j</i>), begins to decrease at 90 minutes (<i>k</i>), and is completely absent in nucleus with relocation back to the cytoplasm at 4 hours, some residual cytoplasmic staining remains visible (<i>l</i>).</p