Understanding the transformation of a single-celled fertilized egg to a highlypatterned embryo with three di stinct axes has long been a goal of developmental biology. The Transforming Growth Factor ~ (TGF-~) family of morphogens have essential roles in many developmental patbways. Nodal, a member of this complex and tightly regulated signalling family is responsible for many of the patterning events taking place in the early vertebrate embryo, including germ layer specification and axis determination. Whi lst many components of this signalling pathway have been identified, the precise levels of control indicate other factors or targets still await identification. A Xenopus induction assay using active a member of the TGF-~ family led to up-regulation of Lrig3. Lrig3 is a single~pass transmembrane protein with a structured extracellular domain containing Leucine Rich Repeats and Immunoglobulin·like domains. The in vitro and in vivo expression of the Lrig gene family (Lrigs 1·3) in the developing mouse embryo and postnatal eNS are investigated. A Lrig3 knock-out mouse was created and analysed and bioinfonnatic data on protein structure and func tion was completed. The expression profiles for Lrig J-3 identify distinct differences in expression domains. Significant but not complete overlap exists between LrigJ and 3 which are expressed together in the primitive streak, node, somites and branchial arches. When combined with £he high degree of structural homology these data suggest that Lrigl 9 • I and 3 are able to compensate for each other. Differing expression is observed in me anterior neural crest, branchial arches, portions of the somite tissue and developing limbs. The Lrig3'/o mouse revealed no identifiable phenotype in the developing or adult mouse reinforcing the strong possibi lity of redundancy in the Lrig gene family. A novel low-complexity region was identified in the intracellular domain of the protein. Three-dimensional structural analysis indicated multiple binding sites in the extracellular portion of Lrig3. Expression of Lrig2 and 3 in the central nervous system indicated potential roles for Lrigs in neural plasticity. Future research should focus on identifying interacting partners for Lrig3 and further investigation of its funct ion by breeding LrigJ';o/Lrig3-1o mice . 10
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:601125 |
| Date | January 2013 |
| Creators | Swift, Rachel D. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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