טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentTajszeydler Yael
SubjectInvolvement of Glycogen Synthase Kinase 3BETA
in the Skeletal Muscle Differentiation
DepartmentDepartment of Medicine
Supervisor Professor Eyal Bengal


Abstract

Glycogen Synthase Kinase 3β (GSK-3β) is involved in the regulation of glycogen synthesis.

But since its discovery,  many research studies proved the involvement of GSK-3β in other functions and intracellular pathways.

GSK-3β is involved and regulated by at least two intracellular pathways: The Insulin pathway and the Wnt pathway. These two pathways are known to participate in the regulation of the skeletal muscle differentiation; Insulin-like growth factors promote proliferation of satellite cells and muscle differentiation, and the Wnt pathway is known to be involved in regulating the expression of the myogenic factors from the MyoD family. Therefore GSK-3β, as part of these pathways, may be involved in the regulation of myogenesis.


We have examined the role of GSK-3β in the skeletal muscle differentiation. Our studies indicate that inhibition of GSK-3β by Lithium Chloride (LiCl) leads to a delayed but more complete cell cycle withdrawal and muscle differentiation. Furthermore, we observed that expression of constitutively active GSK-3β mutant (S9A) inhibits muscle differentiation, whereas expression of an inactive GSK-3β (K85M) induced precocious differentiation in the absence of Insulin.

We also found that inhibition of GSK-3β activity by LiCl can restore, at least partially, the PI3-K dependent myogenesis, inhibited by LY-294002.

Therefore we consider that GSK-3β is playing an important role in muscle differentiation downstream of the insulin pathway.

Moreover, since inhibition of GSK-3β in myoblasts led to increased levels of β-catenin, a downstream effector of the canonical Wnt pathway, we assumed that GSK-3β is a regulator of myogenesis as a downstream effector of the Wnt pathway.