It is generally thought that vertebral patterning and identity are globally determined prior to somite formation. Relatively little is known about the regulators of vertebral specification after somite segmentation. Here, we demonstrated that Ndrg2, a tumor suppressor gene, was dynamically expressed in the presomitic mesoderm (PSM) and at early stage of differentiating somites. Loss of Ndrg2 in mice resulted in vertebral homeotic transformations in thoracic/lumbar and lumbar/sacral transitional regions in a dose-dependent manner. Interestingly, the inactivation of Ndrg2 in osteoblasts or chondrocytes caused defects resembling those observed in Ndrg2-/- mice, with a lower penetrance. In addition, forced overexpression of Ndrg2 in osteoblasts or chondrocytes also conferred vertebral defects, which were distinct from those in Ndrg2-/- mice. These genetic analyses revealed that Ndrg2 modulates vertebral identity in segmented somites rather than in the PSM. At the molecular level, combinatory alterations of the amount of Hoxc8-11 gene transcripts were detected in the differentiating somites of Ndrg2-/- embryos, which may partially account for the vertebral defects in Ndrg2 mutants. Nevertheless, Bmp/Smad signaling activity was elevated in the differentiating somites of Ndrg2-/- embryos. Collectively, our findings unveiled Ndrg2 as a novel regulator of vertebral specification in differentiating somites.
Bibliographical noteFunding Information:
We thank Prof. Baojie Li for providing us with the Actin-Cre mice. We thank Prof. Xiao Yang for providing us the Col1a1 (3.6 kb)-Cre mice. This work was supported by the National Major Fundamental Research 973 program of China under grant ( 2007CB947301 and 2012CB966903 ) and grants from the National Natural Science Foundation of China ( 31171396 , 81121001 and 31100624 ).
- Bmp/Smad signaling
- Differentiating somites
- Homeotic transformation
- Hox genes
- Vertebral patterning