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Abstract
BackgroundMembers of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFβ, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals.ResultsIn this study, we detect and characterize the hitherto unexplored Runx/CBFβ genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFβ-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFβ dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFβ are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors.ConclusionThese results reveal that Runx and CBFβ likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFβ-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.
Highlights
Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFE, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects
The third and fourth exons encoding the C-terminus of the protein do not exhibit sequence similarity to other Runx proteins, nor to any other protein housed in the NCBI GenBank non-redundant database [48]
The second Runt domain (RD) exon of Nematostella is identical in size to the corresponding exon in all deuterostome Runx genes (105 bp) that have been described
Summary
Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFE, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals. In adult mammals, cellular differentiation pathways are activated to replace various cells of the hematopoietic lineage [1], to differentiate ova [2], to develop mature hair follicles [3], and to heal wounds [4] Many such "adult developmental" processes are thought to depend upon stem cells exhibiting varying degrees of developmental potency [5]. Runx factors have been widely shown to play key roles in cell fate determination and the maintenance of stem cell populations [13,14,15]
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