Linked Life Data

20862309

Source:http://linkedlifedata.com/resource/pubmed/id/20862309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-9-23
pubmed:abstractText
A model of the gene-regulatory-network (GRN), governing growth, survival, and differentiation of melanocytes, has emerged from studies of mouse coat color mutants and melanoma cell lines. In this model, Transcription Factor Activator Protein 2 alpha (TFAP2A) contributes to melanocyte development by activating expression of the gene encoding the receptor tyrosine kinase Kit. Next, ligand-bound Kit stimulates a pathway activating transcription factor Microphthalmia (Mitf), which promotes differentiation and survival of melanocytes by activating expression of Tyrosinase family members, Bcl2, and other genes. The model predicts that in both Tfap2a and Kit null mutants there will be a phenotype of reduced melanocytes and that, because Tfap2a acts upstream of Kit, this phenotype will be more severe, or at least as severe as, in Tfap2a null mutants in comparison to Kit null mutants. Unexpectedly, this is not the case in zebrafish or mouse. Because many Tfap2 family members have identical DNA-binding specificity, we reasoned that another Tfap2 family member may work redundantly with Tfap2a in promoting Kit expression. We report that tfap2e is expressed in melanoblasts and melanophores in zebrafish embryos and that its orthologue, TFAP2E, is expressed in human melanocytes. We provide evidence that Tfap2e functions redundantly with Tfap2a to maintain kita expression in zebrafish embryonic melanophores. Further, we show that, in contrast to in kita mutants where embryonic melanophores appear to differentiate normally, in tfap2a/e doubly-deficient embryonic melanophores are small and under-melanized, although they retain expression of mitfa. Interestingly, forcing expression of mitfa in tfap2a/e doubly-deficient embryos partially restores melanophore differentiation. These findings reveal that Tfap2 activity, mediated redundantly by Tfap2a and Tfap2e, promotes melanophore differentiation in parallel with Mitf by an effector other than Kit. This work illustrates how analysis of single-gene mutants may fail to identify steps in a GRN that are affected by the redundant activity of related proteins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1553-7404
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:dateRevised
2011-3-11
pubmed:meshHeading
pubmed-meshheading:20862309-Animals, pubmed-meshheading:20862309-Cell Death, pubmed-meshheading:20862309-Cell Differentiation, pubmed-meshheading:20862309-Cell Lineage, pubmed-meshheading:20862309-Cells, Cultured, pubmed-meshheading:20862309-Embryo, Nonmammalian, pubmed-meshheading:20862309-Gene Expression Regulation, Developmental, pubmed-meshheading:20862309-Humans, pubmed-meshheading:20862309-Melanocytes, pubmed-meshheading:20862309-Melanophores, pubmed-meshheading:20862309-Mice, pubmed-meshheading:20862309-Microphthalmia-Associated Transcription Factor, pubmed-meshheading:20862309-Models, Biological, pubmed-meshheading:20862309-Mutation, pubmed-meshheading:20862309-Organ Specificity, pubmed-meshheading:20862309-Proto-Oncogene Proteins c-kit, pubmed-meshheading:20862309-Transcription Factor AP-2, pubmed-meshheading:20862309-Transcription Factors, pubmed-meshheading:20862309-Transcriptional Activation, pubmed-meshheading:20862309-Zebrafish, pubmed-meshheading:20862309-Zebrafish Proteins
pubmed:year
2010
pubmed:articleTitle
Differentiation of zebrafish melanophores depends on transcription factors AP2 alpha and AP2 epsilon.
pubmed:affiliation
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural