The role of bone morphogenetic proteins in the development of the Xenopus laevis tail

This thesis looks at the role of bone morphogenetic proteins (BMPs) during tail development in Xenopus laevis. BMPs are a group of signalling molecules and their role was studied by inhibiting them from the onset of neurulation to the tailbud stage. A time period in which tissues differentiate and organs develop. Bone Morphogenetic Proteins have been well studied during early development and are involved in establishing the dorso-ventral axis through interactions with the antagonists; Chordin, Noggin and Follistatin. However, the removal of BMP activity results in embryonic death. In order to study the effects of BMP signalling in later development, a transgenic line of Xenopus that allows heat-shock inducible inhibition of BMPs was utilised. The transgene construct consists of the heatshock promoter HSP70, which drives expression of Noggin1, an inhibitor of the BMP signalling pathway. The presence of a post-anal tail is a defining characteristic of chordates. Previous studies have shown an involvement of BMP signaling in initiation of tail bud development. Results in this study demonstrated that continued BMP signaling, throughout neurulation until tail bud stages, was required for the proper development of Xenopus. The inhibition of BMPs during early neurulation in particular, resulted in gross deformation of the embryos. BMP signaling was found to be critical in proper formation of the heart, gastrointestinal tract, eye, proctodeum and the tail. The inhibition of BMPs at the onset of neurulation (stage 13) was sufficient to prevent tail formation in Xenopus embryos. This is likely to be the result of inhibition on the expression of XDelta-1 thought to be a critical component of tail bud initiation. BMP inhibition from stages 14 to 28 resulted in embryos with shortened tails. The extent of truncation declined as inhibition was delayed through these stages. The truncation of tails also coincided with a lack of differentiation of somites and a reduction in the staining of the Notch ligand XDelta-1 in the posterior wall of the tail bud. This suggests a role of BMPs in regulating Notch signaling, a pathway involved in differentiation of somites. A further role of BMPs signaling was identified in excluding the proctodeum from the posterior region of the embryo. Previously the incorporation of the proctodeum into the tail bud region has been described as an ectopic forked tail. Analysis utilising in-situ hybridisation enabled this structure to be correctly identified. This study has shown a continued role of BMPs in the development of the embryo throughout neurulation