VERTEBRATE HOMOLOGS OF TINMAN AND BAGPIPE - ROLES OF THE HOMEOBOX GENES IN CARDIOVASCULAR DEVELOPMENT

In Drosophila, dorsal mesodermal specification is regulated by the hom eobox genes tinman and bagpipe. Vertebrate homologs of tinman and bagp ipe have been isolated in various species. Moreover, there are at lead four different genes related to tinman in the vertebras, which indica tes that this gene has been duplicated during evolution. One of the mu rine homologs of tinman is the cardiac homeobox gene Csx or Nkx2.5. Ge ne targeting of Csx/Nkx2.5 showed that this gene is required for compl etion of the looping morphogenesis of the heart. However, it is not es sential for the specification of the heart cell lineage. Early cardiac development might therefore be regulated by other genes, which may ac t either independently or in concert with Csx/Nkx2.5. Possible candida tes 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 bee n 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 p haryngeal and gut endoderm. In contrast, murine Nkx2.3 is expressed in the gut and pharyngeal arches but not the heart. In zebrafish and chi cken, two new NK-2 class homeoproteins, nkx2.7 nd cNkx2.8, have been i dentified. Zebrafish nkx2.7 is expressed in both, the heart and pharyn geal endoderm. In the chicken, cNkx2.8 is expressed in the heart primo rdia and the primitive heart tube and becomes undetectable after loopi ng. No murine homologs of nkx2.7 or cNkx2.8 have been found so far. Th e overlapping expression pattern of NK2 class homeobox genes in the he art and the pharynx may suggest a common origin of these two organs, i n the Drosophila genome, the tinman gene is linked to another NK famil y gene named bagpipe. A murine homolog of bagpipe, Bax/Nkx3.1, is expr essed in somites, blood vessels, and the male reproductive system duri ng embryogenesis (this study), suggesting that this gene's function ma y be relevant for the development of these organs. A bagpipe homolog i n Xenopus, Xbap, is expressed in the gut masculature and a region of t he facial cartilage during development. in this paper, we discuss mole cular Isms of cardiovascular development with particular emphasis on r oles of transcription factors. (C) 1998 Wiley-Liss, Inc.