Requirements for the kit receptor tyrosine kinase during regeneration of zebrafish fin melanocytes

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 1943-1949 ◽  
Author(s):  
John F. Rawls ◽  
Stephen L. Johnson
Keyword(s):  
Stem Cell ◽  
Embryonic Development ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Cell Populations ◽  
Temperature Sensitive ◽  
Kit Mutation ◽  
Fin Regeneration ◽  
Kit Receptor ◽  
Stem Cell Populations

Embryonic neural crest-derived melanocytes and their precursors express the kit receptor tyrosine kinase and require its function for their migration and survival. However, mutations in kit also cause deficits in melanocytes that make up adult pigment patterns, including melanocytes that re-establish the zebrafish fin stripes during regeneration. As adult melanocytes in mice and zebrafish are generated and maintained by stem cell populations that are presumably established during embryonic development, it has been proposed that adult phenotypes in kit mutants result from embryonic requirements for kit. We have used a temperature-sensitive zebrafish kit mutation to show that kit is required during adult fin regeneration to promote melanocyte differentiation, rather than during embryonic stages to establish their stem cell precursors. We also demonstrate a transient role for kit in promoting the survival of newly differentiated regeneration melanocytes.

scholarly journals Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2422-2430 ◽  
Author(s):  
FC Zeigler ◽  
BD Bennett ◽  
CT Jordan ◽  
SD Spencer ◽  
S Baumhueter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Hematopoietic Stem Cell ◽  
Receptor Tyrosine Kinase ◽  
Lymphoid Cells ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Stem Cell Populations

The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived against the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that do not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the population in G0 when compared with the flk-2/flt-3- positive population. Development of agonist antibodies to the receptor shows a proliferative role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymphoid cells and this effect is enhanced by the addition of kit ligand. These studies serve to further illustrate the importance of the flk-2/flt-3 receptor in the regulation of the hematopoietic stem cell.

scholarly journals Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2422-2430 ◽  
Author(s):  
FC Zeigler ◽  
BD Bennett ◽  
CT Jordan ◽  
SD Spencer ◽  
S Baumhueter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Hematopoietic Stem Cell ◽  
Receptor Tyrosine Kinase ◽  
Lymphoid Cells ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Stem Cell Populations

Abstract The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived against the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that do not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the population in G0 when compared with the flk-2/flt-3- positive population. Development of agonist antibodies to the receptor shows a proliferative role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymphoid cells and this effect is enhanced by the addition of kit ligand. These studies serve to further illustrate the importance of the flk-2/flt-3 receptor in the regulation of the hematopoietic stem cell.

Expression of c-Kit receptor tyrosine kinase and effect on β-cell development in the human fetal pancreas

2007 ◽  
Vol 293 (2) ◽  
pp. E475-E483 ◽  
Author(s):  
Jinming Li ◽  
Jaclyn Quirt ◽  
Hung Quoc Do ◽  
Kristina Lyte ◽  
Fraser Fellows ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Differentiation ◽  
Β Cell ◽  
Hematopoietic Stem ◽  
Insulin Expression ◽  
Kit Receptor

The receptor, c-Kit, and its ligand, stem cell factor (SCF), are critical for hematopoietic stem cell differentiation and have been implicated in the development, function, and survival of rodent islets. Previously, we reported that exogenous SCF treatments of cultured human fetal (14–16 wk fetal age) islet-epithelial clusters enhanced islet cell differentiation and proliferation (Li J, Goodyer CG, Fellows F, Wang R. Int J Biochem Cell Biol 38: 961–972, 2006). In the present study, we examined the expression pattern of c-Kit in early to midgestation human fetal pancreata and the relevance of c-Kit receptor tyrosine kinase for insulin gene expression and β-cell survival. c-Kit is expressed in the intact pancreas in a cell-specific manner, with a significant decrease in immunoreactivity in the duct regions from 8 to 21 wk fetal age, paralleled by a significant increase in expression within endocrine regions. These c-Kit-positive cells are highly proliferative and show frequent coexpression with insulin and glucagon. Treatment of islet-epithelial clusters with anti-ACK45 antibody stimulates c-Kit phosphorylation paralleled by a significant increase in PDX-1 and insulin expression, increased cell proliferation, and reduced β-cell death. In contrast, transient transfection with c-Kit siRNA results in a three- to fourfold decrease in c-Kit, PDX-1, and insulin expression and decreased cell proliferation. This study describes important changes in the distribution and dynamics of c-Kit-expressing cells during human fetal pancreatic neogenesis, suggesting that c-Kit may be a marker for human pancreatic islet progenitor cells. Functional analysis of the c-Kit receptor tyrosine kinase provides evidence that phosphorylation of c-Kit receptor may be involved in mediating early β-cell differentiation and survival.

Zebrafish kit mutation reveals primary and secondary regulation of melanocyte development during fin stripe regeneration

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3715-3724 ◽  
Author(s):  
J.F. Rawls ◽  
S.L. Johnson
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Mutational Analysis ◽  
Adult Zebrafish ◽  
Wild Type ◽  
Kit Mutation ◽  
Fin Regeneration ◽  
Normal Melanocyte ◽  
Kit Receptor ◽  
Early Regeneration ◽  
Secondary Mode

Fin regeneration in adult zebrafish is accompanied by re-establishment of the pigment stripes. To understand the mechanisms underlying fin stripe regeneration and regulation of normal melanocyte stripe morphology, we investigated the origins of melanocytes in the regenerating fin and their requirement for the kit receptor tyrosine kinase. Using pre-existing melanin as a lineage tracer, we show that most fin regeneration melanocytes develop from undifferentiated precursors, rather than from differentiated melanocytes. Mutational analysis reveals two distinct classes of regeneration melanocytes. First, an early regeneration class develops dependent on kit function. In the absence of kit function and kit-dependent melanocytes, a second class of melanocytes develops at later stages of regeneration. This late kit-independent class of regeneration melanocytes has little or no role in wild-type fin stripe development, thus revealing a secondary mode for regulation of fin stripes. Expression of melanocyte markers in regenerating kit mutant fins suggests that kit normally acts after mitf and before dct to promote development of the primary kit-dependent melanocytes. kit-dependent and kit-independent melanocytes are also present during fin stripe ontogeny in patterns similar to those observed during regeneration.

Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 49-56 ◽  
Author(s):  
T. Hirata ◽  
E. Morii ◽  
M. Morimoto ◽  
T. Kasugai ◽  
T. Tsujimura ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Neurite Outgrowth ◽  
Dorsal Root Ganglia ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Dorsal Root ◽  
Mouse Embryos ◽  
Kit Receptor ◽  
Vitro Effect

The c-kit receptor tyrosine kinase is highly expressed by about 10% of the neurons in the dorsal root ganglia (DRGs) of mouse embryos. We investigated the in vitro effect of stem cell factor (SCF), the ligand for c-kit receptor, on DRGs. Recombinant murine SCF (rmSCF) induced the outgrowth of c-kit-positive neurites from DRGs of normal (+/+) embryos. The effect of SCF was dose dependent and completely abolished by anti-c-kit ACK2 monoclonal antibody (mAb). Some neurites whose outgrowth was induced by nerve growth factor (NGF) were c-kit-positive, but anti-NGF mAb did not inhibit the rmSCF-induced neurite outgrowth. rmSCF did not induce neurite outgrowth from DRGs of W/W embryos that did not express c-kit receptors on the cell surface and of W42/W42 mutant embryos that expressed c-kit receptors without tyrosine kinase activity. rmSCF also had a trophic effect on c-kit-positive neurons in the culture of dissociated DRG cells. Most c-kit-positive neurons appeared to respond to NGF as well, and the SCF-responsive subpopulation represented about 10% of NGF-responsive neurons. rmSCF did not support the survival of DRG neurons from embryos of W/W and W42/W42 genotypes. These results suggest that the stimulus through the c-kit receptor tyrosine kinase has an important role in development of the peripheral nervous system.

S1886 Pancreatic Transdifferentiation Induced By Signal Transduction System of c-Kit Receptor Tyrosine Kinase and Its Ligand Stem Cell Factor

2008 ◽  
Vol 134 (4) ◽  
pp. A-287
Author(s):  
Makoto Satake ◽  
Tetsuhiro Hamada ◽  
Guido Eibl ◽  
Kazuhiro Suzumura ◽  
Tadamichi Hirano ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Signal Transduction System ◽  
Kit Receptor

scholarly journals A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

Diabetologia ◽  
2015 ◽  
Vol 58 (4) ◽  
pp. 654-665 ◽  
Author(s):  
Zhi-Chao Feng ◽  
Matthew Riopel ◽  
Alex Popell ◽  
Rennian Wang
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Beta Cells ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Pancreatic Beta Cells ◽  
Kit Receptor

Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl)

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 226-232 ◽  
Author(s):  
Shan Zeng ◽  
Zhiheng Xu ◽  
Stan Lipkowitz ◽  
Jack B. Longley
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Feedback Loop ◽  
Ring Finger ◽  
Negative Feedback Loop ◽  
E3 Ligases ◽  
Kit Receptor ◽  
Cbl Proteins

Abstract Activation of the KIT receptor tyrosine kinase contributes to the pathogenesis of several human diseases, but the mechanisms regulating KIT signaling have not been fully characterized. Here, we show that stem cell factor (SCF), the ligand for KIT, induces the interaction between KIT and Cbl proteins and their mutual degradation. Upon SCF stimulation, KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT. We propose a negative feedback loop controlling the SCF-KIT signaling pathway, in which SCF activates KIT. The activated KIT in turn induces phosphorylation and activation of Cbl proteins. The Cbl proteins then bind and direct the degradation of activated KIT, leading to down-regulation of KIT signaling. (Blood. 2005;105:226-232)

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