Tbx20-related genes, mid and H15, are required for tinman expression, proper patterning, and normal differentiation of cardioblasts in Drosophila.
Tbx20-related T-box genes have been implicated in the regulation of heart development in several vertebrate species. In the present report, we demonstrate that a pair of genes representing Drosophila orthologs of Tbx20, midline (mid) and H15, have important functions during the development of the Drosophila equivalent of the heart, i.e. the dorsal vessel. We show that mid is among the earliest known genes that are specifically expressed in all cardioblasts during early embryogenesis, and H15 expression is subsequently activated in the same cells. Mutant embryos lacking the activity of mid, or both mid and H15, are able to form dorsal vessels with largely normal numbers of cardioblasts and pericardial cells. Furthermore, the mutant cardioblasts express several general cardioblast markers such as Mef2 and Toll at normal levels. However, the expression of tinman (tin), which normally occurs in four out of six cardioblasts in each hemisegment of the dorsal vessel, is almost abolished. Conversely, the expression of the Dorsocross (Doc) T-box genes, which is normally restricted to the two Tin-negative cardioblasts in each hemisegment, is strongly expanded into the majority of cardioblasts in mid mutant and mid+H15-deficient embryos. Altogether, the data from the loss-of-function phenotypes demonstrate that mid, and to a lesser degree H15, have important roles in establishing the metameric patterning of cardioblast identities, but not in specifying cardioblasts as such. Ectopic expression of mid causes ectopic tin expression and, less efficiently, produces extra cardioblasts. We propose that one of the major functions of mid and H15 during cardioblast development is the re-activation of tin expression at a stage when the induction of tin by Dpp in the dorsal mesoderm has ceased. Through this activity, mid and H15 are required for the normal functional diversification of cardioblasts and the expression of tin-dependent terminal differentiation genes within the dorsal vessel.
Reim
Ingolf
I
Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, Box 1020, One Gustave L. Levy Pl., New York, NY 10029, USA.
Mohler
James P
JP
Frasch
Manfred
M
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006321:Heart / Q000196:embryology; D009154:Mutation; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D029721:Drosophila Proteins; C495572:H15 protein, Drosophila; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C495571:mid protein, Drosophila; C109259:pnr protein, Drosophila; C102933:tin protein, Drosophila