The fully linked HTML version of this article has now been published.
Development ePress online publication date 16 Jun 2004
doi: 10.1242/dev.01251
Research article
Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis
Odyssé Michos,
Lia Panman,
Kristina Vintersten,
Konstantin Beier,
Rolf Zeller,
and
Aimée Zuniga*
* Author for correspondence (e-mail: aimee.zuniga{at}unibas.ch)
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.
This article has been cited by other articles:
|
|
|
|
 
A. Jara, C. Chacon, M. E. Burgos, A. Droguett, A. Valdivieso, M. Ortiz, P. Troncoso, and S. Mezzano
Expression of gremlin, a bone morphogenetic protein antagonist,is associated with vascular calcification in uraemia
Nephrol. Dial. Transplant.,
November 21, 2008;
(2008)
gfn611v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Costello, K. Howell, E. Cahill, J. McBryan, M. Konigshoff, O. Eickelberg, S. Gaine, F. Martin, and P. McLoughlin
Lung-selective gene responses to alveolar hypoxia: potential role for the bone morphogenetic antagonist gremlin in pulmonary hypertension
Am J Physiol Lung Cell Mol Physiol,
August 1, 2008;
295(2):
L272 - L284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sun, H. Chen, C. Chen, J. A. Whitsett, Y. Mishina, P. Bringas Jr., J. C. Ma, D. Warburton, and W. Shi
Prenatal Lung Epithelial Cell-Specific Abrogation of Alk3-Bone Morphogenetic Protein Signaling Causes Neonatal Respiratory Distress by Disrupting Distal Airway Formation
Am. J. Pathol.,
March 1, 2008;
172(3):
571 - 582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hoshino, R. Shimizu, S. Ohmori, M. Nagano, X. Pan, O. Ohneda, M. Khandekar, M. Yamamoto, K.-C. Lim, and J. D. Engel
Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT.
Genes Cells,
February 1, 2008;
13(2):
159 - 170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hartwig, D. Bridgewater, V. Di Giovanni, J. Cain, Y. Mishina, and N. D. Rosenblum
BMP Receptor ALK3 Controls Collecting System Development
J. Am. Soc. Nephrol.,
January 1, 2008;
19(1):
117 - 124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Sha, D. Wu, L. Zhang, X. Chen, M. Lei, H. Sun, S. Lin, and J. Lang
Differentially expressed genes in human endometrial endothelial cells derived from eutopic endometrium of patients with endometriosis compared with those from patients without endometriosis
Hum. Reprod.,
December 1, 2007;
22(12):
3159 - 3169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Gazzerro, A. Smerdel-Ramoya, S. Zanotti, L. Stadmeyer, D. Durant, A. N. Economides, and E. Canalis
Conditional Deletion of Gremlin Causes a Transient Increase in Bone Formation and Bone Mass
J. Biol. Chem.,
October 26, 2007;
282(43):
31549 - 31557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Michos, A. Goncalves, J. Lopez-Rios, E. Tiecke, F. Naillat, K. Beier, A. Galli, S. Vainio, and R. Zeller
Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis
Development,
July 1, 2007;
134(13):
2397 - 2405.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Pajni-Underwood, C. P. Wilson, C. Elder, Y. Mishina, and M. Lewandoski
BMP signals control limb bud interdigital programmed cell death by regulating FGF signaling
Development,
June 15, 2007;
134(12):
2359 - 2368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Vaillant, O. Michos, S. Orolicki, F. Brellier, S. Taieb, E. Moreno, H. Te, R. Zeller, and D. Monard
Protease nexin 1 and its receptor LRP modulate SHH signalling during cerebellar development
Development,
May 1, 2007;
134(9):
1745 - 1754.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Dickinson, D. W. Walker, E. M. Wintour, and K. Moritz
Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse
Am J Physiol Regulatory Integrative Comp Physiol,
January 1, 2007;
292(1):
R453 - R461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sun, F.-F. Zhuang, J. E. Mullersman, H. Chen, E. J. Robertson, D. Warburton, Y.-H. Liu, and W. Shi
BMP4 Activation and Secretion Are Negatively Regulated by an Intracellular Gremlin-BMP4 Interaction
J. Biol. Chem.,
September 29, 2006;
281(39):
29349 - 29356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Panman, A. Galli, N. Lagarde, O. Michos, G. Soete, A. Zuniga, and R. Zeller
Differential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling
Development,
September 1, 2006;
133(17):
3419 - 3428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. R. Bowers, J. W. Kim, T. C. Otto, and M. D. Lane
Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: Role of the BMP-4 gene
PNAS,
August 29, 2006;
103(35):
13022 - 13027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Koli, M. Myllarniemi, K. Vuorinen, K. Salmenkivi, M. J. Ryynanen, V. L. Kinnula, and J. Keski-Oja
Bone Morphogenetic Protein-4 Inhibitor Gremlin Is Overexpressed in Idiopathic Pulmonary Fibrosis
Am. J. Pathol.,
July 1, 2006;
169(1):
61 - 71.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. V. Cardoso and J. Lu
Regulation of early lung morphogenesis: questions, facts and controversies
Development,
May 1, 2006;
133(9):
1611 - 1624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Chute, G. G. Muramoto, H. K. Dressman, G. Wolfe, N. J. Chao, and S. Lin
Molecular Profile and Partial Functional Analysis of Novel Endothelial Cell-Derived Growth Factors that Regulate Hematopoiesis
Stem Cells,
May 1, 2006;
24(5):
1315 - 1327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Yang, C.-L. Cai, L. Lin, Y. Qyang, C. Chung, R. M. Monteiro, C. L. Mummery, G. I. Fishman, A. Cogen, and S. Evans
Isl1Cre reveals a common Bmp pathway in heart and limb development.
Development,
April 1, 2006;
133(8):
1575 - 1585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. P. Hill, M. M. Taketo, W. Birchmeier, and C. Hartmann
Multiple roles of mesenchymal {beta}-catenin during murine limb patterning
Development,
April 1, 2006;
133(7):
1219 - 1229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lu, G. Minowada, and G. R. Martin
Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function
Development,
January 1, 2006;
133(1):
33 - 42.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Verheyden, M. Lewandoski, C. Deng, B. D. Harfe, and X. Sun
Conditional inactivation of Fgfr1 in mouse defines its role in limb bud establishment, outgrowth and digit patterning
Development,
October 1, 2005;
132(19):
4235 - 4245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Plisov, M. Tsang, G. Shi, S. Boyle, K. Yoshino, S. L. Dunwoodie, I. B. Dawid, T. Shioda, A. O. Perantoni, and M. P. de Caestecker
Cited1 Is a Bifunctional Transcriptional Cofactor That Regulates Early Nephronic Patterning
J. Am. Soc. Nephrol.,
June 1, 2005;
16(6):
1632 - 1644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Zeller
It Takes Time to Make a Pinky: Unexpected Insights into How SHH Patterns Vertebrate Digits
Sci. Signal.,
November 16, 2004;
2004(259):
pe53 - pe53.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2004
