Published in:
Genome Research, 13 (2003) 6a, Seite 1067-1081
Language:
English
DOI:
10.1101/gr.1097503
ISSN:
1088-9051
Origination:
Footnote:
Description:
In mammals, the uniquemidkine(mdk) gene encodes a secreted heparin-binding growth factor with neurotrophic activity. Here, we show the presence of two functionalmdkgenes namedmdkaandmdkbin zebrafish and rainbow trout. Both midkine proteins are clearly different from the related pleiotrophin, which was also identified in zebrafish and other fishes. Zebrafishmdkaandmdkbgenes map to linkage groups LG7 and LG25, respectively, both presenting synteny to human chromosome 11, in which the unique human orthologmdkis located. At least four other genes unique in mammals are also present as duplicates on LG7 and LG25. Phylogenetic and divergence analyses suggested that LG7/LG25 paralogs includingmdkaandmdkbhave been formed at approximately the same time, early during the evolution of the fish lineage. Hence, zebrafish and rainbow troutmdkaandmdkbmight have been generated by an ancient block duplication, and might be remnants of the proposed fish-specific whole-genome duplication. In contrast to the ubiquitous expression of their mammalian counterpart, zebrafishmdkaandmdkbare expressed in spatially restricted, mostly nonoverlapping patterns during embryonic development and strongly in distinct domains in the adult brain. Ectopic ubiquitous expression of bothmdkgenes in early zebrafish embryos caused completely distinct effects on neural crest and floorplate development. These data indicate thatmdkaandmdkbunderwent functional divergence after duplication. This provides an outstanding model to analyze the molecular mechanisms that lead to differences in pathways regulating the formation of homologous embryonic structures in different vertebrates.