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Home > Mathematics and Science Textbooks > Biology, life sciences > The Emergence of Embryonic Dorsal-Ventral Pattern Through the Interactions of BMP Ligands with Their Receptors and Modulators
The Emergence of Embryonic Dorsal-Ventral Pattern Through the Interactions of BMP Ligands with Their Receptors and Modulators

The Emergence of Embryonic Dorsal-Ventral Pattern Through the Interactions of BMP Ligands with Their Receptors and Modulators


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About the Book

Among all bilaterally symmetric animals so far examined, signaling by the family of Bone Morphogenetic Proteins (BMPs) patterns the embryonic dorsal-ventral (DV) axis. Proper DV patterning relies upon the formation of BMP signaling gradients which arise through the combined activities of a network of extracellular modulators regulating ligand-receptor interactions. In Drosophila, genetic analyses have revealed the contributions of two different classes of BMP type I receptors in propagating signaling from two BMP ligands, and uncovered the role of the evolutionarily conserved secreted factor Twisted gastrulation (Tsg) in modulating BMP signaling. However, in vertebrate embryos, several fundamental, related questions have not been addressed. Through a combination of genetics, overexpression, loss of function, and biochemistry, I examined the activities of Tsg and the BMP type I receptors in the zebrafish embryo, and explored the contributions of dimeric BMP ligands to DV patterning. Previously, overexpression analyses showed that Tsg could either promote or antagonize BMP signaling, depending on the presence of additional extracellular modulators Chordin and Tolloid. This left open the question of which of these roles predominates in the embryo. Using morpholino-based knockdown, I determined that Tsg promotes BMP signaling, cooperating with Tolloid, and acting at least in part independently of the presence of Chordin. Zebrafish embryos express five genes encoding type I BMP receptors. Of these, Alk8 is indispensible for DV patterning, but of the four related BMP type I receptors of the Alk3/6 class, no mutations have been described, and no loss of function study has implicated Alk3/6 in fish DV patterning. By combining analysis of a novel antimorphic alk3a mutant with morpholino-mediated loss of function, I find that these four genes perform overlapping functions during DV patterning, but that the divergent type I receptor Alk8 plays a nonredundant role. I show that only BMP heterodimers are capable of activating signaling in the embryo, and that they function by assembling receptor complexes containing both Alk3/6 and Alk8 polypeptides. I propose that only heterodimers possess sufficient receptor affinity to induce signaling in the presence of extracellular antagonists expressed during DV patterning.


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Product Details
  • ISBN-13: 9781243527899
  • Publisher: Proquest, Umi Dissertation Publishing
  • Publisher Imprint: Proquest, Umi Dissertation Publishing
  • Height: 246 mm
  • Weight: 426 gr
  • ISBN-10: 1243527897
  • Publisher Date: 01 Sep 2011
  • Binding: Paperback
  • Spine Width: 12 mm
  • Width: 189 mm


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