6 nots - 1 September 24, 2008 Lecture 6 Slides 3-6...

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1 September 24, 2008 Lecture 6 Slides 3-6 Supramolecular assembly of type IV collagen revisited Most of the information presented in slides 3-5 was presented in lecture 5. Slides 3-5 re- emphasize that assembly of type IV collagen molecules/protomers is initiated by the interaction between NC1 domains of their constituent α− chains. This triggers the assembly of a triple helix in a “zipper-like” fashion towards the N-terminus. In addition to their nucleating role, the NC1 domains ensure that only the proper α -chains are selected. Binding between NC1 is mediated by a combination of interchain hydrophobic interactions, H-bonds and domain swaps, such as β -strands. The assembly of the triple helix is probably initiated in the ER and completed in the Golgi – although a research paper states that promoter assembly occurs in the Golgi. Dimerization, lateral association and tetramerization occur primarily within extracellular compartments. It remains controversial whether or not covalent bonds are formed the NC1 domains of adjacent protomers after dimerization - some dimers may be covalently cross-linked whereas others may not. Inter- α -chain and intermolecular/inter-protomer disulfide bonds are concentrated in the N-terminal regions where most cysteine residues are found. As noted on slide size, an α 1, α 2, α 5, α 6 network exist in basement membranes (BM) of tissues with elastic properties. See slide 6 for examples. The precise function(s) of the isoform is not known. Type IV collagen and embryonic basal laminae The early development of mammalian embryos (Taken verbatim from Gilbert S (2003) Developmental Biology, 7 th Ed., Sinauer Assoc.). Cleavages in mammalian embryos are among the slowest in the animal kingdom- about 12-24 hours apart. Blastomeres through the 8-cell stage form a loose arrangement with plenty of space between them. Following third cleavage, the blastomeres undergo a spectacular change in their behavior. Cell adhesion proteins such as E-cadherin become expressed, and the blastomeres suddenly huddle together, forming a compact ball of cells. This tightly packed arrangement is stabilized by tight junctions that form between the outside cells of the ball, sealing off the inside sphere. The cells within the sphere form gap junctions, thereby enabling small molecules and ions to pass between them. The cells of the compacted 8-cell embryo divide to produce a 16-cell morula. The morula consists of a small group of internal cells surrounded by a larger group of external cells. Most of the descendents of the external cells become the trophoblasts (trophectoderm) cells. This group of cells produces no embryonic structures. Rather, it forms the tissue of the chorion, the embryonic portion of the placenta. The chorion enables the fetus to get oxygen and nourishment from the mother.
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2 I will not elaborate any further on the formation of extraembryonic tissues since the focus is on the fate of the inner cell mass, a portion of which gives rise to the embryo proper
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This note was uploaded on 09/29/2009 for the course CSB csb327 taught by Professor Ringuitte during the Fall '08 term at University of Toronto- Toronto.

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6 nots - 1 September 24, 2008 Lecture 6 Slides 3-6...

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