טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentDibner Charna
SubjectThe Role of XMeis3 Protein in Xenopus laevis Embryo
Nervous System Development
DepartmentDepartment of Medicine
Supervisor Professor Dale Frank


Abstract

  A new member of MEIS family proteins, XMeis3, a homologue of the Drosophila homothorax (HTH), was cloned from frog Xenopus laevis. I demonstrated for the first time a key role of XMeis3 protein in proper antero-posterior pattern formation in the CNS. XMeis3 “knock-down” by either XMeis3 antimorph protein or antisense morpholino oligonucleotide prevented hindbrain formation with concomitant expansion of anterior neural tissues (Dibner et al., 2001). I demonstrated that XMeis3 protein functions as a transcriptional activator during the neural patterning. This conclusion is further supported by our studies in transgenic flies, suggesting that HTH functions as a transcriptional activator as well (Inbal et al., 2001). I demonstrated that the function of XMeis3 is crucial for other posteriorizing agents (retinoic acid (RA), fibroblast growth factors, and Wnt family proteins) activity. My study strongly suggests that XMeis3 and RA signaling differentially interact during hindbrain patterning. I have identified HoxD1 as an XMeis3 early target gene, which may in turn regulate XMeis3 activity (Dibner et al., paper in preparation). Meis and Hox proteins interact in causing myeloid leukemia in mammals. Thus, the dissection of the molecular events underlying regulation of early neural cell behavior by XMeis3 may help to unravel the mechanisms leading to tumor formation in cells aberrantly expressing Meis3/Hox genes.