Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development.
One of the first morphological manifestations of left/right (L/R) asymmetry in mammalian embryos is a pronounced rightward looping of the linear heart tube. The direction of looping is thought to be controlled by signals from an embryonic L/R axial system. We report here that morphological L/R asymmetry in the murine heart first became apparent at the linear tube stage as a leftward displacement of its caudal aspect. Beginning at the same stage, the basic helix-loop-helix (bHLH) factor gene eHand was expressed in a strikingly left-dominant pattern in myocardium, reflecting an intrinsic molecular asymmetry. In hearts of embryos lacking the homeobox gene Nkx2-5, which do not loop, left-sided eHand expression was abolished. However, expression was unaffected in Sc1-/- hearts that loop poorly because of hematopoietic insufficiency, and was right-sided in hearts of inv/inv embryos that display situs inversus. The data predict that eHand expression is enhanced in descendants of the left heart progenitor pool as one response to inductive signaling from the L/R axial system, and that eHand controls intrinsic morphogenetic pathways essential for looping. One aspect of the intrinsic response to L/R information falls under Nkx2-5 homeobox control.
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The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
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D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005838:Genotype; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology*; D018257:Helix-Loop-Helix Motifs; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008957:Models, Genetic; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D014018:Tissue Distribution; D014157:Transcription Factors / Q000096:biosynthesis*; D029867:Xenopus Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C095572:Hand1 protein, mouse; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; C097341:helix-loop-helix protein, eHAND