The skeleton is one of the most important features for the
The skeleton is one of the most important features for the reconstruction of vertebrate phylogeny but few data are available to understand its molecular origin. in hard cartilage of hagfish. In dogfish and were expressed in embryonal cartilage whereas all three genes were detected in teeth and placoid scales. In cephalochordates (lancelets) and were strongly expressed in the gill bars and expression of and was found in endo- as well as ectodermal cells. Furthermore we demonstrate that the lancelet Runt protein binds to binding sites in the lancelet promoter and regulates its activity. Together, these results suggest that and were part of a core gene network for cartilage formation, which was already active in the gill bars of the common ancestor of cephalochordates and vertebrates and diversified after duplications had occurred during vertebrate evolution. The similarities in expression patterns of genes support the view that teeth and placoid scales evolved from a homologous developmental module. Author Summary Important molecular mechanisms underlying mammalian skeletogenesis have been described but knowledge about the evolutionary origin of these gene networks is limited. The gene family (deficient mice completely lack bone. and are essential for cartilage development and Runx2 regulates the key factor Indian hedgehog, which coordinates skeletogenesis. Here, we reconstructed Runt gene evolution in correlation to skeletal evolution. By analyzing lancelets, one of the closest living relatives of vertebrates, we revealed that the single and family founder genes were co-expressed in primitive skeletal elements of the chordate stem species. 23277-43-2 supplier Interestingly, at this stage the and pathways were already directly linked to one another. Furthermore we isolated two genes from a 23277-43-2 supplier representative of jawless cartilaginous fish (hagfish) and three genes from jawed cartilaginous fish (dogfish) which were all expressed in cartilage. The dogfish genes were also found in teeth and placoid scales. This study suggests that genes were involved in all ancient processes of chordate skeletogenesis. Furthermore the analysis supports the theory that most likely the gut was the tissue that originally secreted an acellular gill gut skeleton in the chordate ancestor. Introduction The skeleton is a hallmark of vertebrates and has been widely used over the past decades for phylogenetic analyses . However, little is known about its molecular evolution. Descriptive data are available for the matrix proteins produced by the cells that constitute the skeleton in jawless vertebrates (epitomized by hagfish and lampreys, collectively termed agnathans). Beside species specific proteins  they possess cartilage with type II collagen (in mammals, was shown to be expressed in cartilage of the lamprey . Interestingly (an invertebrate homolog to the mammalian gene expression has been described in skeletal elements of lancelets, agnathans and jawed cartilaginous fish in 23277-43-2 supplier spite of the fact that Runt transcription factors (synonyms: gene has two 23277-43-2 supplier isoforms with different N-termini starting with a MASNS-like motif under the distal P1 promoter and a MRIPV sequence under the proximal Promoter P2. Furthermore the 3 end has a conserved VWRPY-motif . is indispensable for osteogenesis as mice bearing a homozygous mutation in completely lack bone , and is together with essential for cartilage differentiation ,. Futhermore Runx2 directly regulates the key signaling molecule (((haploinsufficiency causes the human bone disease cleidocranial dysplasia, further substantiating its importance for skeletal development . Importantly, all three mammalian genes are expressed in cartilage and have been shown to play a role in the formation and differentiation of skeletal elements ,,. Furthermore, all genes in the mouse are involved in tooth formation . In contrast to the extensively studied genes, which are 23277-43-2 supplier important for patterning, genes are essential for features that represent evolutionary innovations of vertebrates such as bone . Such innovations result from tinkering with existing processes, from the flexibility that arises from modifications to existing gene networks, and from selective advantage provided by gene duplications or modifications . As simply as this theory explains an important evolutionary process, as difficult it is to functionally analyze how Rab7 the genetic networks underlying innovations like the vertebrate skeleton evolved. Based on the central role of genes for skeletogenesis in higher vertebrates we.