Removal of Stem Cell Factor or Addition of Monoclonal Anti-c-KIT Antibody Induces Apoptosis in Murine Melanocyte Precursors

Ito, Masaru; Kawa, Yoko; Ono, Hirotake; Okura, Mitsuhiro; Baba, Takao; Kubota, Yasuo; Nishikawa, Sin Ichi; Mizoguchi, Masahiro

doi:10.1046/j.1523-1747.1999.00552.x

Cited by 88 publications

(75 citation statements)

References 21 publications

(27 reference statements)

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“…Data from other cell types dependent on SCF-Kit interactions and the current microarray results suggest that control of intrinsic apoptosis may be one important mechanism. For example, mast cells (30), melanocytes (19), and a subset of natural killer cells (6) express Kit, and its engagement with SCF is associated with increased expression of Bcl-2, an anti-intrinsic apoptosis protein. In the current microarray results, the expression of Bcl2 is elevated in both classes of ICC (Tables 13 and 14).…”

Section: Table 10 Genes Related To Ion Channel and Ion Transport Thamentioning

confidence: 99%

Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine

Chen¹,

Ördög²,

Chen³

et al. 2007

Physiological Genomics

106

153

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cells of Cajal (ICC) have important functions in regulation of motor activity in the gastrointestinal tract. In murine small intestine, ICC are gathered in the regions of the myenteric plexus (ICC-MY) and the deep muscular plexus (ICC-DMP). These two classes of ICC have different physiological functions. ICC-MY are pacemaker cells and generate the slow-wave electrical rhythmicity of gastrointestinal organs. ICC-DMP form synaptic connections with the varicose nerve terminals of enteric motor neurons and are involved in reception and transduction of motor neurotransmission. Gene expression underlying specific functions of ICC classes is incompletely understood. In the present study, we used recently developed highly selective techniques to isolate the two functional ICC classes from enzymatically dispersed intestinal muscles by fluorescence-activated cell sorting. The transcriptomes of ICC-MY and ICC-DMP were investigated using oligonucleotide microarray analysis. Differential expression of functional groups of genes defined by standard gene ontology terms was also studied. There were substantial numbers of genes expressed more abundantly in ICC than in the tunica muscularis, and we also detected marked phenotypic differences between ICC-MY and ICC-DMP. Notably, genes related to cell junction, process guidance, and vesicle trafficking were upregulated in ICC. Consistent with their specific functions, metabolic and Ca 2ϩ transport genes were relatively upregulated in ICC-MY, whereas genes for signaling proteins involved in transduction of neurotransmitter functions were relatively upregulated in ICC-DMP. Our results may lead to the identification of novel biomarkers for ICC and provide directions for further studies designed to understand ICC function in health and disease.Affymetrix Mouse Genome 430.2 GeneChips; Bioconductor; enteric nervous system; ion channel; signal transduction MOTOR PATTERNS of the gastrointestinal (GI) tract require the coordinated contractions of the smooth muscle cell component of the organs. One level of coordination comes from the fact that the smooth muscle cells are electrically coupled, and their electrical activity is driven by pacemaker cells known as interstitial cells of Cajal (ICC) that lie in the plane of the myenteric plexus between the circular and longitudinal muscle layers (ICC-MY) (16, 58). ICC-MY are electrically coupled to each other via gap junctions and form a network of cells that extends around the circumference and along the length of the small intestine (1, 39, 58). The ICC-MY network is electrically coupled to smooth muscle cells of both layers, providing a low-resistance pathway for the conduction of pacemaker activity to the musculature (9). ICC-MY possess the ionic conductances necessary to initiate electrical slow waves and to propagate these events actively (cf. Ref. 43).A second level of control of GI motor function comes from the intrinsic motor neurons arising from enteric ganglia. Both inhibitory and excitatory motor neurons innervate the muscle layers, an...

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Section: Table 10 Genes Related To Ion Channel and Ion Transport Thamentioning

confidence: 99%

Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine

Chen¹,

Ördög²,

Chen³

et al. 2007

Physiological Genomics

106

153

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“…S4 in the supplementary material). Therefore, Kitl-dependent proliferation and survival of follicular melanocytes (Botchkareva et al, 2001;Ito et al, 1999) is probably dependent on Notch1 activity in keratinocytes.…”

Section: Bi-compartmental Signals Also Impact Melanocyte Populationsmentioning

confidence: 99%

Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes

et al. 2007

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Notch1-deficient epidermal keratinocytes become progressively hyperplastic and eventually produce tumors. By contrast, Notch1-deficient hair matrix keratinocytes have lower mitotic rates, resulting in smaller follicles with fewer cells. In addition, the ratio of melanocytes to keratinocytes is greatly reduced in hair follicles. Investigation into the underlying mechanism for these phenotypes revealed significant changes in the Kit, Tgfβ and insulin-like growth factor (IGF) signaling pathways, which have not been previously shown to be downstream of Notch signaling. The level of Kitl (Scf) mRNA produced by Notch1-deficient follicular keratinocytes was reduced when compared with wild type, resulting in a decline in melanocyte population. Tgfβ ligands were elevated in Notch1-deficient keratinocytes, which correlated with elevated expression of several targets,including the diffusible IGF antagonist Igfbp3 in the dermal papilla. Diffusible stromal targets remained elevated in the absence of epithelial Tgfβ receptors, consistent with paracrine Tgfβ signaling. Overexpression of Igf1 in the keratinocyte reversed the phenotype, as expected if Notch1 loss altered the IGF/insulin-like growth factor binding protein(IGFBP) balance. Conversely, epidermal keratinocytes contained less stromal Igfbp4 and might thus be primed to experience an increase in IGF signaling as animals age. These results suggest that Notch1 participates in a bi-compartmental signaling network that controls homeostasis, follicular proliferation rates and melanocyte population within the skin.

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“…11B) (Cable et al, 1995;Okura et al, 1995;Ito et al, 1999) and during the differentiation of zebrafish melanoblasts into melanophores in the regenerating fin ).…”

Section: Chromatophore Stem Cells During Post-embryonic Developmentmentioning

confidence: 99%

Temporal and cellular requirements for Fms signaling during zebrafish adult pigment pattern development

2003

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Ectothermic vertebrates exhibit a diverse array of adult pigment patterns. A common element of these patterns is alternating dark and light stripes each comprising different classes of neural crest-derived pigment cells. In the zebrafish, Danio rerio, alternating horizontal stripes of black melanophores and yellow xanthophores are a prominent feature of the adult pigment pattern. In fms mutant zebrafish, however, xanthophores fail to develop and melanophore stripes are severely disrupted. fmsencodes a type III receptor tyrosine kinase expressed by xanthophores and their precursors and is the closest known homologue of kit, which has long been studied for roles in pigment pattern development in amniotes. In this study we assess the cellular and temporal requirements for Fms activity in promoting adult pigment pattern development. By transplanting cells betweenfms mutants and either wild-type or nacre mutant zebrafish,we show that fms acts autonomously to the xanthophore lineage in promoting the striped arrangement of adult melanophores. To identify critical periods for fms activity, we isolated temperature sensitive alleles of fms and performed reciprocal temperature shift experiments at a range of stages from embryo to adult. These analyses demonstrate that Fms is essential for maintaining cells of the xanthophore lineage as well as maintaining the organization of melanophore stripes throughout development. Finally, we show that restoring Fms activity even at late larval stages allows essentially complete recovery of xanthophores and the development of a normal melanophore stripe pattern. Our findings suggest that fms is not required for establishing a population of precursor cells during embryogenesis but is required for recruiting pigment cell precursors to xanthophore fates,with concomitant effects on melanophore organization.

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Removal of Stem Cell Factor or Addition of Monoclonal Anti-c-KIT Antibody Induces Apoptosis in Murine Melanocyte Precursors

Cited by 88 publications

References 21 publications

Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine

Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine

Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes

Temporal and cellular requirements for Fms signaling during zebrafish adult pigment pattern development

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