Expression of doublecortin reveals articular chondrocyte lineage in mouse embryonic limbs

The doublecortin (Dcx) gene encodes a microtubule-binding protein that was originally found in immature neurons. In this study, we used two mouse strains that express reporter genes (LacZ and enhanced green fluorescence protein, respectively) driven by the endogenous Dcx promoter. We found that Dcx was expressed in the mesenchymal cells in the mouse embryonic limb buds. A population of the mesenchymal cells continued Dcx expression after they differentiated into joint interzone cells and then articular chondrocytes. In contrast, the endochondral chondrocytes lost Dcx expression when the mesenchymal cells differentiated into endochondral chondrocytes. These data support a concept that the articular and endochondral chondrocytes originate from the same mesenchymal cells that express Dcx. In contrast to the notion that articular chondrocytes are derived from de-differentiated endochondral chondrocytes, our findings demonstrate that the lineages of articular and endochondral chondrocytes bifurcate at the stage of endochondral chondrogenesis.     

3′-Untranslated region of doublecortin mRNA is a binding target of the Musashi1 RNA-binding protein

Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem cells, and is considered to be a stemness factor. A known function of Msi1 is translational repression of specifically bound mRNAs. Although the basic mechanism and some target RNAs have been reported, further survey of interactors is necessary to understand the integrated function of Msi1. By screening using an mRNA display technique, we found that doublecortin (dcx) mRNA is a specific binding target of Msi1 in vitro. We confirmed that Msil repressed translation of a luciferase reporter gene linked to the selected 3′-untranslated region fragment of dcx in Neuro2A cells.