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Kit signaling is involved in melanocyte stem cell fate decisions in zebrafish embryos.

ABSTRACT: Adult stem cells are crucial for growth, homeostasis and repair of adult animals. The melanocyte stem cell (MSC) and melanocyte regeneration is an attractive model for studying regulation of adult stem cells. The process of melanocyte regeneration can be divided into establishment of the MSC, recruitment of the MSC to produce committed daughter cells, and the proliferation, differentiation and survival of these daughter cells. Reduction of Kit signaling results in dose-dependent reduction of melanocytes during larval regeneration. Here, we use clonal analysis techniques to develop assays to distinguish roles for these processes during zebrafish larval melanocyte regeneration. We use these clonal assays to investigate which processes are affected by the reduction in Kit signaling. We show that the regeneration defect in kita mutants is not due to defects in MSC recruitment or in the proliferation, differentiation or survival of the daughter cells, but is instead due to a defect in stem cell establishment. Our analysis suggests that the kit MSC establishment defect results from inappropriate differentiation of the MSC lineage.

SUBMITTER: O'Reilly-Pol T

PROVIDER: S-EPMC3583038 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Kit signaling is involved in melanocyte stem cell fate decisions in zebrafish embryos.

O'Reilly-Pol Thomas T Johnson Stephen L SL

Development (Cambridge, England) 20130130 5

Adult stem cells are crucial for growth, homeostasis and repair of adult animals. The melanocyte stem cell (MSC) and melanocyte regeneration is an attractive model for studying regulation of adult stem cells. The process of melanocyte regeneration can be divided into establishment of the MSC, recruitment of the MSC to produce committed daughter cells, and the proliferation, differentiation and survival of these daughter cells. Reduction of Kit signaling results in dose-dependent reduction of mel ...[more]

PMID: 23364331

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Project description:The retention of particular genes after the whole genome duplication in zebrafish has given insights into how genes may evolve through partitioning of ancestral functions. We examine the partitioning of expression patterns and functions of two zebrafish kit ligands, kit ligand a (kitla) and kit ligand b (kitlb), and discuss their possible coevolution with the duplicated zebrafish kit receptors (kita and kitb). In situ hybridizations show that kitla mRNA is expressed in the trunk adjacent to the notochord in the middle of each somite during stages of melanocyte migration and later expressed in the skin, when the receptor is required for melanocyte survival. kitla is also expressed in other regions complementary to kita receptor expression, including the pineal gland, tail bud, and ear. In contrast, kitlb mRNA is expressed in brain ventricles, ear, and cardinal vein plexus, in regions generally not complementary to either zebrafish kit receptor ortholog. However, like kitla, kitlb is expressed in the skin during stages consistent with melanocyte survival. Thus, it appears that kita and kitla have maintained congruent expression patterns, while kitb and kitlb have evolved divergent expression patterns. We demonstrate the interaction of kita and kitla by morpholino knockdown analysis. kitla morphants, but not kitlb morphants, phenocopy the null allele of kita, with defects for both melanocyte migration and survival. Furthermore, kitla morpholino, but not kitlb morpholino, interacts genetically with a sensitized allele of kita, confirming that kitla is the functional ligand to kita. Last, we examine kitla overexpression in embryos, which results in hyperpigmentation caused by an increase in the number and size of melanocytes. This hyperpigmentation is dependent on kita function. We conclude that following genome duplication, kita and kitla have maintained their receptor-ligand relationship, coevolved complementary expression patterns, and that functional analysis reveals that most or all of the kita receptor's function in the embryo are promoted by its interaction with kitla.

Project description:Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions) can also trigger a cell-autonomous Notch signal (cis-signaling), whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability. Our study exemplifies the complexity of regulations when multiple signaling sources share the same receptor and provides the tools for their characterization.

Dataset Information

Kit signaling is involved in melanocyte stem cell fate decisions in zebrafish embryos.

Publications

Kit signaling is involved in melanocyte stem cell fate decisions in zebrafish embryos.

Similar Datasets

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