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Coming Events

9/8/2014 - Contemporary Biochemistry - Sandy Schmid
 
9/12/2014 - IPiB Retreat
 
9/14/2014 - UMDF Energy Run
 

Kimble Lab - Regulatory network controlling the decision between self-renewal and differentiation

We have discovered a molecular network that controls the decision between self-renewal and differentiation in animal germ cells. Briefly, GLP-1/Notch signaling promotes self-renewal, at least in part, by activating expression of two nearly identical and functionally redundant proteins, FBF-1 and FBF-2.  The FBF proteins repress gene expression by controlling translation or stability of target mRNAs. Together, FBF-1 and FBF-2 provide a major network hub that represses expression of differentiation regulators. GLD-1 is a translational repressor, and GLD-2 a translational activator. The switch from self-renewal into differentiation therefore relies on the concerted downregulation of self-renewal and upregulation of differentiation. The major role of RNA regulatory proteins in this network was not expected, but all are conserved, and some are broadly used stem cell regulators. This work provides the first glimpse of how these conserved regulators work together in a network to govern the selection between self-renewal and differentiation.

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