TY - JOUR
T1 - Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11
AU - McPherron, Alexandra C.
AU - Lawler, Ann M.
AU - Lee, Se Jin
N1 - Funding Information:
We thank P. Dunlap for assistance with maintenance of mice; A. Boulet and M. Capecchi for providing Hox clones; and D. Nathans, M. Capecchi, P. Beachy and E. Hsiao for discussions. This work was supported by research grant R01H035887 from the NIH (S.-J.L.). The early phase of this work was supported by grants from the Edward Mallinckrodt, Jr. Foundation and MetaMorphix, Inc. (S.-J.L).
PY - 1999/7
Y1 - 1999/7
N2 - The bones that comprise the axial skeleton have distinct morphological features characteristic of their positions along the anterior/posterior axis. We previously described a novel TGF-β family member, myostatin (encoded by the gene Mstn, formerly Gdf8), that has an essential role in regulating skeletal muscle mass. We also identified a gene related to Mstn by low- stringency screening. While the work described here was being completed, the cloning of this gene, designated Gdf11 (also called Bmp11), was also reported by other groups. Here we show that Gdf11, a new transforming growth factor β (TGFβ) superfamily member, has an important role in establishing this skeletal pattern. During early mouse embryogenesis, Gdf11 is expressed in the primitive streak and tail bud regions, which are sites where new mesodermal cells are generated. Homozygous mutant mice carrying a targeted deletion of Gdf11 exhibit anteriorly directed homeotic transformations throughout the axial skeleton and posterior displacement of the hindlimbs. The effect of the mutation is dose dependent, as Gdf11(+/-) mice have a milder phenotype than Gdf11(-/-) mice. Mutant embryos show alterations in patterns of Hox gene expression, suggesting that Gdf11 acts upstream of the Hox genes. Our findings suggest that Gdf11 is a secreted signal that acts globally to specify positional identity along the anterior/posterior axis.
AB - The bones that comprise the axial skeleton have distinct morphological features characteristic of their positions along the anterior/posterior axis. We previously described a novel TGF-β family member, myostatin (encoded by the gene Mstn, formerly Gdf8), that has an essential role in regulating skeletal muscle mass. We also identified a gene related to Mstn by low- stringency screening. While the work described here was being completed, the cloning of this gene, designated Gdf11 (also called Bmp11), was also reported by other groups. Here we show that Gdf11, a new transforming growth factor β (TGFβ) superfamily member, has an important role in establishing this skeletal pattern. During early mouse embryogenesis, Gdf11 is expressed in the primitive streak and tail bud regions, which are sites where new mesodermal cells are generated. Homozygous mutant mice carrying a targeted deletion of Gdf11 exhibit anteriorly directed homeotic transformations throughout the axial skeleton and posterior displacement of the hindlimbs. The effect of the mutation is dose dependent, as Gdf11(+/-) mice have a milder phenotype than Gdf11(-/-) mice. Mutant embryos show alterations in patterns of Hox gene expression, suggesting that Gdf11 acts upstream of the Hox genes. Our findings suggest that Gdf11 is a secreted signal that acts globally to specify positional identity along the anterior/posterior axis.
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U2 - 10.1038/10320
DO - 10.1038/10320
M3 - Article
C2 - 10391213
AN - SCOPUS:0033052036
SN - 1061-4036
VL - 22
SP - 260
EP - 264
JO - Nature genetics
JF - Nature genetics
IS - 3
ER -