title: Xenopus eHAND: a marker for the developing cardiovascular system of the embryo that is regulated by bone morphogenetic proteins.
abstract: The bHLH protein eHAND is a sensitive marker for cardiovascular precursors in the Xenopus embryo. The earliest site of expression is a broad domain within the lateral plate mesoderm of the tailbud embryo. This domain comprises precursors that contribute to the posterior cardinal veins in later stages. Surprisingly, expression is profoundly asymmetric at this stage and is random with respect to embryo side. XeHAND is also expressed in an anterior domain that encompasses the prospective heart region. Within the myocardium and pericardium, transcripts are also asymmetrically distributed, but in these tissues they are localised in a left-sided manner. Later in development XeHAND transcripts are largely restricted to the ventral aorta, aortic arches and venous inflow tract (sinus venosus) which flank the heart itself, but no expression is detected in neural crest derivatives at any stage. This demonstrates that patterns of XeHAND expression differ markedly amongst vertebrates and that in Xenopus, XeHAND expression identifies all of the earliest formed elements of the cardiovascular system. In animal cap explants, expression of XeHAND (but not other markers of cardiogenic differentiation) is strongly induced by ectopic expression of the TGFbeta family members, BMP-2 and BMP-4, but this can be blocked by coexpression of a dominant negative BMP receptor. This suggests that XeHAND expression in the embryo is regulated by the ventralising signals of bone morphogenetic proteins. High levels of expression are also detected in explants treated with high doses of activin A which induces cardiac muscle differentiation. No such effect is seen with lower doses of activin, indicating that a second pathway may regulate the XeHAND gene during cardiogenesis.
authors.affiliation: Division of Developmental Biology, National Institute for Medical Research, London, UK.
authors.forename: D B
authors.initials: DB
authors.lastname: Sparrow
authors.forename: S
authors.initials: S
authors.lastname: Kotecha
authors.forename: N
authors.initials: N
authors.lastname: Towers
authors.forename: T J
authors.initials: TJ
authors.lastname: Mohun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002319:Cardiovascular System / Q000196:embryology*; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005819:Genetic Markers; D006321:Heart / Q000196:embryology / Q000254:growth & development; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014981:Xenopus / Q000196:embryology* / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D014157:Transcription Factors; C095572:Hand1 protein, mouse; C097341:helix-loop-helix protein, eHAND