Coles, Edward George; (2002) Identification and analysis of a novel cysteine rich protein. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

During neurulation the hindbrain forms a series of transient segments termed rhombomeres (r) that underlie subsequent head development, but gaps remain in understanding of this process. This thesis describes a whole mount in situ hybridisation screen of a subtracted chick cDNA hindbrain library to identify further genes with potential roles during hindbrain development. The expression patterns of 445 randomly chosen clones have been analysed and 39 (9 %) of the cDNA clones were found to exhibit restricted expression within developing hindbrain tissue and/or adjacent tissue. Of these, 3 clones were identified that have previously characterised roles during hindbrain development. Nine clones identified in this screen encode molecules that are identical to or closely related to proteins with previously unknown roles in early embryonic neural development and 27 encode for proteins of unknown functions. One of the clones, 0B7/cE13, was identified during the in situ screen due to its expression pattern in the dorsal neural tube during the period of neural crest emergence. Analysis of the predicted peptide sequence suggests that cE13 is a secreted protein, that has a number of cysteine-rich repeat motifs found in bone morphogenetic protein (BMP) binding proteins. Detailed analysis of the expression pattern of E13 in both the chick and mouse shows that it is co-expressed or expressed in adjacent tissues compared with some members of the BMP signalling family in a number of embryonic tissues. Biochemical experiments demonstrate that chick cE13 binds BMP-4 and functional analysis in Xenopus embryos shows that cE13 promotes the induction of Xhox3 expression by BMP-4. These findings implicate cE13 with a BMP modulating activity. Since BMPs have been implicated in neural crest cell induction, initiation of migration, and apoptosis, this suggests a role for E13 in regulating aspects of neural crest development by BMPs.

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