PT  - JOURNAL ARTICLE
AU  - Michos, Odyssé
AU  - Panman, Lia
AU  - Vintersten, Kristina
AU  - Beier, Konstantin
AU  - Zeller, Rolf
AU  - Zuniga, Aimée
TI  - <em>Gremlin</em>-mediated BMP antagonism induces the
epithelial-mesenchymal feedback signaling controlling metanephric kidney and
limb organogenesis
AID  - 10.1242/dev.01251
DP  - 2004 Jul 15
TA  - Development
PG  - 3401--3410
VI  - 131
IP  - 14
4099  - http://dev.biologists.org/content/131/14/3401.short
4100  - http://dev.biologists.org/content/131/14/3401.full
SO  - Development2004 Jul 15; 131
AB  - Epithelial-mesenchymal feedback signaling is the key to diverse organogenetic processes such as limb bud development and branching morphogenesis in kidney and lung rudiments. This study establishes that the BMP antagonist gremlin (Grem1) is essential to initiate these epithelial-mesenchymal signaling interactions during limb and metanephric kidney organogenesis. A Grem1 null mutation in the mouse generated by gene targeting causes neonatal lethality because of the lack of kidneys and lung septation defects. In early limb buds, mesenchymal Grem1 is required to establish a functional apical ectodermal ridge and the epithelial-mesenchymal feedback signaling that propagates the sonic hedgehog morphogen. Furthermore, Grem1-mediated BMP antagonism is essential to induce metanephric kidney development as initiation of ureter growth, branching and establishment of RET/GDNF feedback signaling are disrupted in Grem1-deficient embryos. As a consequence, the metanephric mesenchyme is eliminated by apoptosis, in the same way as the core mesenchymal cells of the limb bud.