|M.Sc Student||Rojtblat Adi|
|Subject||The Role of the Transcription Factor Myocyte Enhancer|
Factor 2(mef2)in Mesodermal and Neuro-Ectodermal
Induction in Xenopus Laevis Embryos
|Department||Department of Medicine||Supervisor||ASSOCIATE PROF. Eyal Bengal|
|Full Thesis text|
During the blastula stage Xenopus laevis embryos begin, for the first time, to perform transcriptional processes. This phenomenon is named the Mid Blastula Transition (MBT). The first genes to be transcribed are active in the induction and differentiation of the three embryonic germ layers: endoderm, mesoderm and ectoderm and in the induction of a dorsal signaling center, the Spemann organizer. Their expression is regulated by factors of maternal origin.
The transcription factor Myocyte Enhancer Factor 2 (MEF2) plays a central role in transcriptional circuits that regulate cell differentiation and organogenesis of many different tissues in a vast range of organisms.Nonthless, little research has been conducted regarding a possible role for this transcription factor in early embryonic developmental processes.
In this work we have demonstrated that Xenopus MEF2 isoforms A and D (XMef2A, XMef2D) are both of maternal origin, and that transcripts of both isoforms, as well as the XMef2D protein, are expressed during early developmental stages, prior to and following the MBT. We have analysed the activity of XMef2D by antisense morpholino-mediated knockdown, as well as by expression of an activated Mef2-VP16 chimera protein. Our results designate a role for XMef2D in induction of the mesoderm during blastula, and at later stages of the Spemann organizer and neural ectoderm.
We have localized the expression of XMef2D to the animal hemisphere of the embryos before the MBT and show that its expression expands to the marginal and vegetal zones following the MBT. We propose a model according to which mesoderm is induced at the marginal zone following the MBT due to the joint activity of XMef2D and mesoderm-inducing factors downstream of the vegetal transcription factor VegT. We show that the activity of both transcription factors, VegT and XMef2D is required for mesodermal induction and for the formation of the Spemann organizer. Furthermore, we have demonstrated that Mef2 is capable of binding four elements in the promoter of Xnr1, a nodal family member involved in mesodermal induction downstream of VegT.