No. 8/August 18, 2003
From hydras to humans - only few signaling pathways control the development of living beings
Over the past five to ten years, biologists have gained increasingly deeper insights into biochemical and molecular networks regulating the development of living beings, from the fertilized egg to complete organisms containing billions of cells and different organs. “We established that from hydras (freshwater polyps) to humans only a handful of signaling pathways control this development”, commented Prof. Walter Birchmeier, Research Group Leader at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. He added, “the signaling paths fit in precisely with each other, preventing any maldevelopment or tumor formation”. Together with Natalia Soshnikova, a PhD student from his research group, he has now been able to demonstrate in mice that two particular signaling pathways are required for the formation of limb. “Both signaling pathways are equally important and depend on each other. If one of them is missing, limbs cannot form”, commented the researchers. At the same time, they succeeded in tracking the timely sequence and the associated formation of the limbs (axis formation). The research by Natalia Soshnikova, Dr. Dietmar Zechner und Prof. Birchmeier carried out in collaboration with researchers in the USA and Japan, has now been published in the renowned journal Genes and Development (Vol. 16, No. 17, August 15, 2003, pp. 1963-1968) and online http://www.genesdev.org/cgi/doi/10.1101/gad.263003.
Natalia Soshnikova investigated the development of limbs in mice in the so-called ectoderm, the outer epithelial layer of the body. Apart from limbs, this cell layer is also responsible for the formation of other organs such as skin, hair, claws and sensory organs, the brain and the spinal column. Two signaling pathways with the technical term BMP pathway and Wnt pathway are required for the formation of the different axes of the limbs. The abbreviation BMP stands for bone morphogenic protein, whilst Wnt stands for “wingless type“, describing a certain change in the fruit-fly Drosophila melanogaster. The Birchmeier research group has been researching molecules of the Wnt signaling pathway, containing also the so-called beta-catenin, for years. Beta-catenin also plays a decisive roll for the formation of “cell kits” for cells, thus ensuring that the cells stay in their cell union.
The two signaling pathways are responsible for the formation of two axes of limbs, the shoulder axis – claw tip (proximal – distal) or the paw back axis – inside paw surface (dorsal – ventral). The young researcher Natalia Soshnikova established that the BMP pathway initially applies the signals for the formation of the axis from the shoulder to the claw tip (proximal – distal). After this process, the Wnt-signaling pathway becomes active. Also, the signaling molecule beta-catenin from the Wnt signaling pathway becomes active first for the formation of the axis paw back - inside paw surface (dorsal – ventral) followed by those of the BMP pathways. The findings of the Development Biologist are also of importance for research into the nervous and cardiovascular system as well as the formation of tumors.
*Genetic
interaction between Wnt/β-catenin and BMP receptor signaling during
formation of the AER and the dorsal-ventral axis in the limb. Natalia Soshnikova1, Dietmar Zechner1,
Joerg Huelsken1,5, Yuji Mishina2,6, Richard R. Behringer2, Makoto M. Taketo3, E. Bryan Crenshaw III4 and Walter Birchmeier1* 1Max-Delbrück
Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany. 2Department
of Molecular Genetics, University of Texas M.D. Anderson Cancer Center,
Houston, Texas 77030, USA. 3Department
of Pharmacology, Kyoto University Graduate School of Medicine,
Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. 4Mammalian
Neurogenetics Group, Center for Childhood Communication, Children's Hospital of
Philadelphia, Philadelphia, PA 19104, USA. 5Present
address: ISREC, Chemin des Boveresses 155, 1066 Epalinges s/ Lausanne,
Switzerland. 6Present
address: Laboratory of Reproductive and Developmental Toxicology, National
Institute of Environmental Health Sciences, Research Triangle Park, North
Carolina 27709, USA. Short title: β-Catenin and BMP receptor
in limb
Barbara Bachtler
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