טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentHarduf Haggar
SubjectExpression of Sef during Avian Embryogenesis and its
Regulation in Limb Development
DepartmentDepartment of Biology
Supervisors Professor Dina Ron
Mr. Reshef Ram


Abstract

The signaling pathways leading to growth and patterning of various organs are tightly controlled during the development of any organism. These control mechanisms usually involve the utilization of feedback and pathway specific antagonists where the pathway induces the expression of its own antagonist. Sef is a feedback antagonist of FGF signaling, which has been recently identified in Zebrafish and mammals. Here we report the isolation of chicken Sef (cSef), and demonstrate the conserved nature of the regulatory relationship with FGF-signaling. In chick embryos, Sef is expressed in a pattern that coincides with many known sites of FGF signaling. In the developing limb, cSef is expressed in the mesoderm underlying the apical ectodermal ridge (AER) in the region known as the progress zone. Chick Sef message first appeared after limb budding and AER formation, it persisted until differentiation begins, thereafter it faded to almost undetectable levels when differentiation was clearly apparent. Gain- and loss of function experiments showed that FGFs differentially regulate the expression of cSef in various tissues. Thus, removal of the AER down regulated cSef expression, and FGF2 but not FGF4 or FGF8 beads substituted for the AER in maintaining cSef expression. At sites were cSef is not normally expressed, FGF4 and FGF2, but not FGF8 beads, induced cSef expression. Our results provide new insights into the relationship between FGFs and their negative regulators and point to FGF2 as a prime candidate in regulating cSef expression during normal limb development. In addition, the kinetics of cSef expression during limb development suggests its role in regulating limb outgrowth but not limb initiation.