|M.Sc Student||Katz Sandra|
|Subject||The Role of the Mef2D Transcription Factor in Mesodern and|
Ectoderm Specification During Early Development
|Department||Department of Medicine||Supervisor||Professor Eyal Bengal|
|Full Thesis text|
In Xenopus, specification of the three germ layers is one of the earliest developmental decisions occurring prior to gastrulation. During the first twelfth cell cycles zygotic transcription is repressed, and maternally expressed factors provide the blueprint for embryonic development. Only then, at a stage called mid-blastula transition (MBT), zygotic transcription is initiated. The first genes to be transcribed are active in the formation and specification of the three germ layers, ectoderm, mesoderm, and endoderm, and in the induction of the dorsal signaling center, the Spemann-Mangold organizer. Their expression is regulated by maternal factors.
Here we focused on the roles of the Mef2D transcription factor at early development. We report that Mef2D is expressed in the animal hemisphere before MBT, and at the initiation of zygotic transcription, its expression expands into the marginal region that gives rise to mesoderm. Knockdown of Mef2D delayed gastrulation movements, prevented embryo elongation at the subsequent tailbud stage and caused severe defects in axial tissues of mesoderm and ectoderm origin. Knockdown of Mef2D reduced the expression of genes involved in mesoderm formation and patterning. Our analyses indicate that Mef2D and FGF signaling function in a positive feedback loop in the marginal region that is necessary to maintain mesodermal gene expression. One target gene of Mef2D in the mesoderm is Xnr1 of the Nodal family, which serves as a mediator of some of Mef2D mesodermal activities. In the animal region Mef2D is necessary for the expression of early ectodermal markers, as well as neural and epidermal markers at later stages. In addition, we find that Mef2D plays a role in the epithelial nature of ectoderm cells and in the maintenance of their pluripotency that is demonstrated by their ability to respond to different inducing signals.
In sum, our results indicate that marginally expressed Mef2D protein is a key transcription factor in mesoderm specification at late blastula stages, while animally expressed Mef2D protein induces the expression of pro-ectodermal genes effecting cell adhesion properties and competence to respond to external signals.