טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentAamar Emil
SubjectThe Role of XMeis3 Protein in Anterior-Posterior Pattern
Formation During Early Embryo Development in
Xenopus laevis
DepartmentDepartment of Medicine
Supervisor Professor Dale Frank


Abstract

Meis proteins have been shown to be involved in cell fate decisions in both the vertebrate and invertebrate peripheral and central nervous systems. In this study, we wanted to determine how XMeis3 protein mechanistically controls cell fate decisions in the hindbrain. Our knockdown studies in Xenopus embryos, have demonstrated a strong requirement for the XMeis3 gene in proper formation and patterning of the hindbrain. The XMeis3 protein acts as a caudalizer, inducing posterior neural marker expression in the absence of neural induction; this caudalizing activity is dependent on the presence of FGF/MAP kinase signaling. In recombinant explant assays, the XMeis3 expressing tissue induced mesoderm-independent cell elongations in adjacent juxtaposed neuralized explants. These elongated explants expressed the Krox20 and HoxB3 (hindbrain), n-tubulin (primary neuron) and HoxB9 (spinal cord) markers. Expression of the otx2 and XAG-1 (anterior markers) was severely inhibited in the elongated explants. These cell elongations were neural and not mesodermal in origin. No muscle actin or notochord was detected in the elongating explants. Posterior gene expression and cell elongations were dependent on the presence of FGF/MAP kinase signaling and Wnt PCP activity. Rescue experiments suggest that XMeis3 activates FGF/MAP kinase which in turn regulates PCP signaling. Thus XMeis3 protein can act in a cell non-autonomous manner to trigger a signaling cascade, which induces posterior neural marker expression and cell morphogenesis in the developing CNS. XMeis3 likely acts to establish a hindbrain induction center that regulates early A-P cell fate in the brain.