Review: melanocyte migration and survival controlled by SCF/c-kit expression.

Melanocytes are derived from neural crest and migrate along the dorsolateral pathway to colonize the final destination in the skin. Stem cell factor and its receptor c-kit were identified as gene products of Sl and W mutant loci; both of them were known to have defects in melanocytes survival. In this review, we focus on the function of stem cell factor and c-kit in melanocyte migration and survival, which has become clearer in the last decade. By analysis of both molecules in wild-type and white spotting mutant mice, ligand and receptor set were shown to play multiple roles in the development of melanocytes in mouse ontogeny. Functional blockade of c-kit by specific monoclonal antibody illustrated distinct c-kit dependent and independent stages in melanocyte development. Finally, SCF transgene expression demonstrated that part of the c-kit dependent step is regulated by spatiotemporally specific ligand expression and also indicated the presence of c-kit independent melanocyte stem cells in postnatal skin.

Regulation of E- and P-cadherin expression correlated with melanocyte migration and diversification.

Melanocytes (Mc) and their progenitors melanoblasts (Mb) are derived from the neural crest and migrate along the dorsolateral pathway to colonize the dermis, the epidermis, and finally the hair matrix. To examine the involvement of cadherins in the migration of Mc lineage cells, we combined flow cytometric analysis of dissociated live cells with immunohistochemical staining of tissue sections to quantify the level of cadherin expression on the surface of Mb/Mc. At 11.5 days postcoitum, Mb are in the dermis and are E-cadherin(-)P-cadherin(-) (E-cad(-)P-cad(-)). During the next 48 h, a 200-fold increase of E-cadherin expression is induced on the surface of Mb prior to their entry into the epidermis, thereby forming a homogeneous E-cad(high)P-cad(-/low) population. The cadherin expression pattern then diversifies, giving rise to three populations, an E-cad(-)P-cad(-) dermal population, E-cad(high)P-cad(low) epidermal population, and E-cad(-)P-cad(med-high) follicular population. In all three populations, the patterns of expression are region-specific, being identical with those of surrounding cells such as keratinocytes and fibroblasts, and are preserved before and after pigmentation. While most of the epidermal Mb/Mc disappear after the neonatal stage in normal mice, forced expression of steel factor in the epidermis of transgenic mice promotes survival of epidermal Mb/Mc, maintaining epidermal-type cadherin expression pattern (E-cad(high)P-cad(low)) throughout the postnatal life. These findings indicate the involvement of extrinsic cues in coordinating the cadherin expression pattern of Mb/Mc and suggest a role for E- and P-cadherins in guiding Mc progenitors to their final destinations.

Detection of pulmonary emboli at the segmental and subsegmental level with electron-beam CT: validation in a porcine model.

RATIONALE AND OBJECTIVES: The authors evaluated the sensitivity of electron-beam computed tomography (CT) in the detection of segmental and subsegmental pulmonary artery emboli in a porcine model. MATERIALS AND METHODS: Twenty-one segmental and subsegmental branch pulmonary arteries in five swine were selectively catheterized and embolized with gelatin sponge pledgets. The presence of emboli was confirmed by means of contrast material-enhanced angiography. Contrast-enhanced CT scans of the pulmonary arteries were then obtained with 3-mm collimation, 2-mm table travel between sections, and an imaging time of 100 msec per section. Contrast material was injected at a rate of 2-3 mL/sec, depending on the animal's weight, with a total dose of 60 mL for each scan. Cardiac-gated and nongated scans were obtained, but breath holding was not possible in these animals. RESULTS: Contrast-enhanced electron-beam CT scanning allowed correct prospective identification of 18 of 21 emboli in the segmental and subsegmental branches of the pulmonary arteries. The overall sensitivity was 86%. Cardiac gating subjectively improved image quality but did not result in greater sensitivity in the detection of emboli. The level of sensitivity was not affected by the use of breath holding. CONCLUSION: Contrast-enhanced electron-beam CT is a sensitive method for the detection of embolism in the segmental and subsegmental pulmonary arteries.