Growth differentiation factor 11 locally controls anterior–posterior patterning of the axial skeleton. Issue 12 (10th June 2019)

• Record Type: Journal Article
• Authors: Suh, Joonho; Eom, Je‐Hyun; Kim, Na‐Kyung; Woo, Kyung Mi; Baek, Jeong‐Hwa; Ryoo, Hyun‐Mo; Lee, Se‐Jin; Lee, Yun‐Sil
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 12(2019:Dec.)
• Page Start: 23360
• Page End: 23368
• Publication Date: 2019-06-10
• Subjects: Cdx2‐Cre -- GDF11 -- skeletal patterning -- tail bud; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28904
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Growth and differentiation factor 11 (GDF11) is a transforming growth factor β family member that has been identified as the central player of anterior–posterior (A–P) axial skeletal patterning. Mice homozygous for Gdf11 deletion exhibit severe anterior homeotic transformations of the vertebrae and craniofacial defects. During early embryogenesis, Gdf11 is expressed predominantly in the primitive streak and tail bud regions, where new mesodermal cells arise. On the basis of this expression pattern of Gdf11 and the phenotype of Gdf11 mutant mice, it has been suggested that GDF11 acts to specify positional identity along the A–P axis either by local changes in levels of signaling as development proceeds or by acting as a morphogen. To further investigate the mechanism of action of GDF11 in the vertebral specification, we used a Cdx2‐Cre transgene to generate mosaic mice in which Gdf11 expression is removed in posterior regions including the tail bud, but not in anterior regions. The skeletal analysis revealed that these mosaic mice display patterning defects limited to posterior regions where Gdf11 expression is deficient, whereas displaying normal skeletal phenotype in anterior regions where Gdf11 is normally expressed. Specifically, the mosaic mice exhibited seven true ribs, a pattern observed in wild‐type ( wt ) mice (vs. 10 true ribs in Gdf11 −/− mice), in the anterior axis and nine lumbar vertebrae, a pattern observed in Gdf11 null mice (vs. six lumbar vertebrae in wt mice), in the posterior axis. Our findings suggest that GDF11, rather than globally acting as a morphogen secreted from the tail bud, locally regulates axial vertebral patterning. Abstract : Gdf11, a transforming growth factor β family member that regulates axial skeletal patterning, is predominantly expressed in the tail bud during developmental stages, leading to the belief that growth and differentiation factor 11 (GDF11) acts to specify positional identity along the anterior–posterior axis either by local changes in levels of signaling as development proceeds or by acting as a morphogen. Our results show that mosaic mice, in which Gdf11 expression is removed exclusively in posterior regions including the tail bud, display patterning defects limited to posterior regions, suggesting that GDF11, rather than acting at long range as a morphogen secreted from the tail bud, locally regulates axial patterning.