title: Ndrg2 regulates vertebral specification in differentiating somites.
abstract: 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.
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, China.
authors: Huang
authors: H
authors: Zhu
authors: Jianzhi
authors: J
authors: Zhao
authors: Wenrong
authors: W
authors: Zhou
authors: Hanjun
authors: H
authors: Li
authors: Rujiang
authors: R
authors: Zhou
authors: Lingling
authors: L
authors: Zhang
authors: Haixia
authors: H
authors: Zhao
authors: Jingjing
authors: J
authors: Cao
authors: Xuming
authors: X
authors: Zhu
authors: Hongliang
authors: H
authors: Hu
authors: Gang
authors: G
authors: Ma
authors: Lin
authors: L
authors: He
authors: Zhengju
authors: Z
authors: Yao
authors: Libo
authors: L
authors: Yao
authors: Xizhi
authors: X
authors: Guo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005801:Genes, Homeobox; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019170:Somites / Q000196:embryology* / Q000378:metabolism*; D013131:Spine / Q000196:embryology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; C485172:Ndr2 protein, mouse; D011506:Proteins; D025521:Tumor Suppressor Proteins