Vertebrate homologs of tinman and bagpipe: roles of the homeobox genes in cardiovascular development.
In Drosophila, dorsal mesodermal specification is regulated by the homeobox genes tinman and bagpipe. Vertebrate homologs of tinman and bagpipe have been isolated in various species. Moreover, there are at least four different genes related to tinman in the vertebrate, which indicates that this gene has been duplicated during evolution. One of the murine homologs of tinman is the cardiac homeobox gene Csx or Nkx2.5. Gene targeting of Csx/Nkx2.5 showed that this gene is required for completion of the looping morphogenesis of the heart. However, it is not essential for the specification of the heart cell lineage. Early cardiac development might therefore be regulated by other genes, which may act either independently or in concert with Csx/Nkx2.5. Possible candidates might be other members of the NK2 class of homeobox proteins like Tix/Nkx2.6, Nkx2.3, nkx2.7, or cNkx2.8. Murine Tix/Nkx2.6 mRNA has been detected in the heart and pharyngeal endoderm (this study). Xenopus XNkx2.3 and chicken cNkx2.3 are expressed in the heart as well as in pharyngeal and gut endoderm. In contrast, murine Nkx2.3 is expressed in the gut and pharyngeal arches but not the heart. In zebrafish and chicken, two new NK-2 class homeoproteins, nkx2.7 and cNkx2.8, have been identified. Zebrafish nkx2.7 is expressed in both, the heart and pharyngeal endoderm. In the chicken, cNkx2.8 is expressed in the heart primordia and the primitive heart tube and becomes undetectable after looping. No murine homologs of nkx2.7 or cNkx2.8 have been found so far. The overlapping expression pattern of NK2 class homeobox genes in the heart and the pharynx may suggest a common origin of these two organs. In the Drosophila genome, the tinman gene is linked to another NK family gene named bagpipe. A murine homolog of bagpipe, Bax/Nkx3.1, is expressed in somites, blood vessels, and the male reproductive system during embryogenesis (this study), suggesting that this gene's function may be relevant for the development of these organs. A bagpipe homolog in Xenopus, Xbap, is expressed in the gut masculature and a region of the facial cartilage during development. In this paper, we discuss molecular mechanisms of cardiovascular development with particular emphasis on roles of transcription factors.
Tanaka
M
M
Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Kasahara
H
H
Bartunkova
S
S
Schinke
M
M
Komuro
I
I
Inagaki
H
H
Lee
Y
Y
Lyons
G E
GE
Izumo
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002319:Cardiovascular System / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005801:Genes, Homeobox; D017344:Genes, Insect; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D017386:Sequence Homology, Amino Acid; D014714:Vertebrates / Q000196:embryology / Q000235:genetics*