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Developmental Biology
Article
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2006
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2006 . Peer-reviewed
License: Elsevier Non-Commercial
Data sources: Crossref
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Hedgehog and RAS pathways cooperate in the anterior–posterior specification and positioning of cardiac progenitor cells

Authors: Liu, Jiandong; Qian, Li; Wessells, Robert J.; Bidet, Yannick; Jagla, Krzysztof; Bodmer, Rolf;

Hedgehog and RAS pathways cooperate in the anterior–posterior specification and positioning of cardiac progenitor cells

Abstract

The Drosophila heart is a highly ordered structure with only a limited number of cell types, which are arranged in a stereotyped metameric pattern. Ras signaling has previously been implicated in contributing to heart formation, but how positional information is integrated with this pathway to specify, distinguish and precisely position individual cardiac progenitors within the presumptive heart-forming region are not known. Here, we present evidence that the striped pattern of the secreted factor Hedgehog (Hh), in combination with the RAS pathway, specifies and positions neighboring groups of cardiac progenitors within each segment: the anterior ladybird (lbe)- and the posterior even skipped (eve)-expressing cardiac progenitors. Loss of hh function (while maintaining wg activity) results in the absence of the Eve cells, whereas the Lbe cells are expanded within the cardiac mesoderm. Overexpressing the repressor form of Cubitus interruptus (Ci), a Hh pathway antagonist, also results in expansion of Lbe at the expense of Eve, as does lowering Ras signaling. Conversely, overexpression of Hh or increasing Ras signaling eliminates Lbe expression while expanding Eve within the cardiogenic mesoderm. Increasing Ras signaling in the absence of Hh suggests that the Ras pathway is in part epistatic to Hh. Hh controls dorsal mesodermal Ras signaling by transcriptional regulation of the EGF receptor ligand protease, encoded by rhomboid (rho). Conversely, Hh overexpression can fully inhibit Lbe even when Ras signaling is much reduced, suggesting that Hh also acts in parallel to Ras. We propose that the Eve precursors next to the Hh stripe are distinguished from more distant Lbe precursors by locally augmenting Ras signaling via elevating rho transcripts. Thus, the spatial precision of cell type specification within an organ depends on multiple phases of inductive interaction between the ectoderm and the mesoderm.

Keywords

Male, Cell specification, Animals, Genetically Modified, Mesoderm, Ectoderm, Animals, Drosophila Proteins, Hedgehog Proteins, Molecular Biology, Crosses, Genetic, In Situ Hybridization, Body Patterning, Cell Proliferation, Homeodomain Proteins, Cardiogenesis, Gene Expression Regulation, Developmental, Epistasis, Genetic, Heart, Cell Biology, Immunohistochemistry, Ladybird, DNA-Binding Proteins, Even-skipped, Drosophila melanogaster, Gene Expression Regulation, Drosophila, Female, Developmental Biology

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
29
Average
Average
Top 10%
hybrid