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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-4-3
pubmed:abstractText
The pitx2 gene is a member of the bicoid-homeodomain class of transcription factors that has been implicated in the control of left-right asymmetry during organogenesis. Here we demonstrate that in zebrafish there are two pitx2 isoforms, pitx2a and pitx2c, which show distinct expression patterns and have non-overlapping functions during mesendoderm and asymmetric organ development. pitx2c is expressed symmetrically in presumptive mesendoderm during late blastula stages and in the prechordal plate during late gastrulation. pitx2a expression is first detected at bud stage in the anterior prechordal plate. The regulation of early mesendoderm pitx2c expression is dependent on one-eyed pinhead (EGF-CFC-related gene) and spadetail (tbx-transcription factor) and can be induced by ectopic goosecoid expression. Maintenance of pitx2c midline expression is dependent on cyclops (nodal) and schmalspur, but not no tail (brachyury). Ectopic expression of pitx2 isoforms results in distinct morphological and molecular phenotypes, indicating that pitx2a and pitx2c have divergent regulatory functions. Both isoforms downregulate goosecoid on the dorsal side, but in contrast to earlier reports that nodal and lefty are upstream of pitx2, ectopic pitx2c in other regions induces cyclops, lefty2 and goosecoid expression. Asymmetric isoform expression occurs in non-overlapping domains, with pitx2c in left dorsal diencephalon and developing gut and pitx2a in left heart primordium. Targeted asymmetric expression in Xenopus shows that both isoforms can alter left-right development, but pitx2a has a slightly stronger effect on heart laterality. Our results indicate that distinct genetic pathways regulate pitx2a and pitx2c isoform expression, and each isoform regulates different downstream pathways during mesendoderm and asymmetric organ development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1081-93
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10662647-Amino Acid Sequence, pubmed-meshheading:10662647-Animals, pubmed-meshheading:10662647-Body Patterning, pubmed-meshheading:10662647-Brain, pubmed-meshheading:10662647-Embryo, Nonmammalian, pubmed-meshheading:10662647-Endoderm, pubmed-meshheading:10662647-Evolution, Molecular, pubmed-meshheading:10662647-Heart, pubmed-meshheading:10662647-Homeodomain Proteins, pubmed-meshheading:10662647-Humans, pubmed-meshheading:10662647-Intestines, pubmed-meshheading:10662647-Mesoderm, pubmed-meshheading:10662647-Molecular Sequence Data, pubmed-meshheading:10662647-Nuclear Proteins, pubmed-meshheading:10662647-Paired Box Transcription Factors, pubmed-meshheading:10662647-Promoter Regions, Genetic, pubmed-meshheading:10662647-Protein Isoforms, pubmed-meshheading:10662647-Sequence Alignment, pubmed-meshheading:10662647-Sequence Homology, Amino Acid, pubmed-meshheading:10662647-Transcription Factors, pubmed-meshheading:10662647-Xenopus, pubmed-meshheading:10662647-Zebrafish
pubmed:year
2000
pubmed:articleTitle
Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms.
pubmed:affiliation
Huntsman Cancer Institute, Center for Children, University of Utah, Salt Lake City, UT 84112, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't