Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis

Development (Cambridge) - Tập 131 Số 14 - Trang 3401-3410 - 2004
Odyssé Michos1,2, Lia Panman1, Kristina Vintersten3, Konstantin Beier4, Rolf Zeller2, Aimée Zúñiga2
1Department of Developmental Biology, Utrecht University, Padualaan 8,NL-3584CH Utrecht, The Netherlands
2Developmental Genetics, Dept. of Clinical-Biological Sciences (DKBW),University of Basel Medical School, c/o Anatomy Institute, Pestalozzistrasse 20, CH-4056 Basel, Switzerland
3Transgenic Service, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
4Department of Histology, Anatomy Institute, Pestalozzistrasse 20, CH-4056 Basel, Switzerland

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Affolter, M., Bellusci, S., Itoh, N., Shilo, B., Thiery, J.-P. and Werb, Z. (2003). Tube or not tube: remodeling epithelial tissues by branching morphogenesis. Dev. Cell4, 11-18.

Avsian-Kretchmer, O. and Hsueh, A. J. (2003). Comparative genomic analysis of the eight-membered-ring cystine-knot-containing bone morphogenetic protein (BMP) antagonists. Mol. Endocrinol.18,1-12.

Barrow, J. R., Thomas, K. R., Boussadia-Zahui, O., Moore, R.,Kemler, R., Capecchi, M. R. and McMahon, A. P. (2003). Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge. Genes Dev.17,394-409.

Capdevila, J., Tsukui, T., Rodriquez Esteban, C., Zappavigna, V. and Izpisua Belmonte, J. C. (1999). Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin. Mol. Cell4, 839-849.

Dono, R., Texido, G., Dussel, R., Ehmke, H. and Zeller, R.(1998). Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. EMBO J.17,4213-4225.

Drossopoulou, G., Lewis, K. E., Sanz-Ezquerro, J. J., Nikbakht,N., McMahon, A. P., Hofmann, C. and Tickle, C. (2000). A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling. Development127,1337-1348.

Dudley, A. T., Lyons, K. M. and Robertson, E. J.(1995). A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev.9,2795-2807.

Dudley, A. T. and Robertson, E. J. (1997). Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev. Dyn.208,349-362.

Dudley, A. T., Ros, M. A. and Tabin, C. J.(2002). A re-examination of proximodistal patterning during vertebrate limb development. Nature418,539-544.

Evangelista, M., Zigmond, S. and Boone, C.(2003). Formins: signaling effectors for assembly and polarization of actin filaments. J. Cell Sci.116,2603-2611.

Gupta, I. R., Piscione, T. D., Grisaru, S., Phan, T.,Macias-Silva, M., Zhou, X., Whiteside, C., Wrana, J. L. and Rosenblum,N. D. (1999). Protein kinase A is a negative regulator of renal branching morphogenesis and modulates inhibitory and stimulatory morphogenetic proteins. J. Biol. Chem.274,26305-26314.

Haramis, A. G., Brown, J. M. and Zeller, R.(1995). The limb deformity mutation disrupts the SHH/FGF-4 feedback loop and regulation of 5′HoxD genes during limb pattern formation. Development121,4237-4245.

Hellmich, H. L., Kos, L., Cho, E. S., Mahon, K. A. and Zimmer,A. (1996). Embryonic expression of glial cell-line derived neurotrophic factor (GDNF) suggests multiple developmental roles in neural differentiation and epithelial-mesenchymal interactions. Mech. Dev.54,95-105.

Hsu, D., Economides, A., Wang, X., Eimon, P. and Harland, R.(1998). The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol. Cell5,673-683.

Kawakami, Y., Capdevila, J., Buscher, D., Itoh, T., Rodriguez Esteban, C. and Izpisua Belmonte, J. C. (2001). WNT signals control FGF-dependent limb initiation and AER induction in the chick embryo. Cell104,891-900.

Khokha, M. K., Hsu, D., Brunet, L. J., Dionne, M. S. and Harland, R. M. (2003). Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nat. Genet.34,303-307.

Kreidberg, J. A., Sariola, H., Loring, J. M., Maeda, M.,Pelletier, J., Housman, D. and Jaenisch, R. (1993). WT-1 is required for early kidney development. Cell74,679-691.

Lewandoski, M., Sun, X. and Martin, G. R.(2000). Fgf8 signalling from the AER is essential for normal limb development. Nat. Genet.26,460-463.

Lu, M. M., Yang, H., Zhang, L., Shu, W., Blair, D. G. and Morrisey, E. E. (2001). The bone morphogenetic protein antagonist gremlin regulates proximal-distal patterning of the lung. Dev. Dyn.222,667-680.

Luo, G., Hofmann, C., Bronckers, A. L., Sohocki, M., Bradley, A. and Karsenty, G. (1995). BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev.9,2808-2820.

Maas, R., Elfering, S., Glaser, T. and Jepeal, L.(1994). Deficient outgrowth of the ureteric bud underlies the renal agenesis phenotype in mice manifesting the limb deformity (ld) mutation. Dev. Dyn.199,214-228.

Martin, G. R. (1998). The roles of FGFs in the early development of vertebrate limbs. Genes Dev.12,1571-1586.

Martinez, G. and Bertram, J. F. (2003). Organisation of bone morphogenetic proteins in renal development. Nephron Exp. Nephrol.93,e18-e22.

Merino, R., Rodriguez-Leon, J., Macias, D., Ganan, Y.,Economides, A. N. and Hurle, J. M. (1999). The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb. Development126,5515-5522.

Miyazaki, Y., Oshima, K., Fogo, A., Hogan, B. L. and Ichikawa,I. (2000). Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter. J. Clin. Invest.105,863-873.

Moon, A. M. and Capecchi, M. R. (2000). Fgf8 is required for outgrowth and patterning of the limbs. Nat. Genet.26,455-459.

Nishinakamura, R., Matsumoto, Y., Nakao, K., Nakamura, K., Sato,A., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Scully, S., Lacey,D. L. et al. (2001). Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development128,3105-3115.

Pachnis, V., Mankoo, B. and Costantini, F.(1993). Expression of the c-ret proto-oncogene during mouse embryogenesis. Development119,1005-1017.

Panman, L. and Zeller, R. (2003). Patterning the limb before and after SHH signalling. J. Anat.202, 3-12.

Pearce, J. J., Penny, G. and Rossant, J.(1999). A mouse cerberus/Dan-related gene family. Dev. Biol.209,98-110.

Pizette, S. and Niswander, L. (1999). BMPs negatively regulate structure and function of the limb apical ectodermal ridge. Development126,883-894.

Pizette, S., Abate-Shen, C. and Niswander, L.(2001). BMP controls proximodistal outgrowth, via induction of the apical ectodermal ridge, and dorsoventral patterning in the vertebrate limb. Development128,4463-4474.

Raatikainen-Ahokas, A., Hytonen, M., Tenhunen, A., Sainio, K. and Sariola, H. (2000). BMP-4 affects the differentiation of metanephric mesenchyme and reveals an early anterior-posterior axis of the embryonic kidney. Dev. Dyn.217,146-158.

Riddle, R. D., Johnson, R. L., Laufer, E. and Tabin, C.(1993). Sonic hedgehog mediates the polarizing activity of the ZPA. Cell75,1401-1416.

Sanz-Ezquerro, J. J. and Tickle, C. (2000). Autoregulation of Shh expression and Shh induction of cell death suggest a mechanism for modulating polarising activity during chick limb development. Development127,4811-4823.

Saxén, L. (1987). Organogenesis of the Kidney. Cambridge, UK: Cambridge University Press.

Shi, W., Zhao, J., Anderson, K. D. and Warburton, D.(2001). Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching morphogenesis. Am. J. Physiol. Lung Cell Mol. Physiol.280,L1030-L1039.

Soshnikova, N., Zechner, D., Huelsken, J., Mishina, Y.,Behringer, R. R., Taketo, M. M., Crenshaw, E. B., 3rd and Birchmeier,W. (2003). Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb. Genes Dev.17,1963-1968.

Sun, X., Mariani, F. V. and Martin, G. R.(2002). Functions of FGF signalling from the apical ectodermal ridge in limb development. Nature418,501-508.

te Welscher, P., Zuniga, A., Kuijper, S., Drenth, T., Goedemans,H. J., Meijlink, F. and Zeller, R. (2002). Progression of vertebrate limb development through SHH-mediated counteraction of GLI3. Science298,827-830.

Tickle, C. (2003). Patterning systems–from one end of the limb to the other. Dev. Cell4,449-458.

Torres, M., Gomez-Pardo, E., Dressler, G. R. and Gruss, P.(1995). Pax-2 controls multiple steps of urogenital development. Development121,4057-4065.

Towers, P. R., Woolf, A. S. and Hardman, P.(1998). Glial cell line-derived neurotrophic factor stimulates ureteric bud outgrowth and enhances survival of ureteric bud cells in vitro. Exp. Nephrol.6,337-351.

Vainio, S. and Lin, Y. (2002). Coordinating early kidney development: lessons from gene targeting. Nat. Rev. Genet.3,533-543.

Zeller, R., Haramis, A., Zuniga, A., McGuigan, C., Dono, R.,Davidson, G., Chabanis, S. and Gibson, T. (1999). Formin defines a large family of morphoregulatory genes and functions in establishment of the polarising region. Cell Tissue Res.296,85-93.

Zuniga, A., Haramis, A. P., McMahon, A. P. and Zeller, R.(1999). Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds. Nature401,598-602.

Zuniga, A., Michos, O., Spitz, F., Haramis, A. P. G., Panman,L., Galli, A., Vintersten, K., Klasen, C., Mansfield, W., Kuc, S.,Duboule, D., Dono, R. and Zeller, R. (2004). Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression. Genes Dev (in press).

Thông tin
Thông tin xuất bản

Development (Cambridge)

Tập 131 Số 14

3401-3410

Thông tin tác giả