Growth factors co-ordinate to stimulate nephron progenitor stem cells

Growth factors co-ordinate to stimulate nephron progenitor stem cells

Self-renewal of nephron progenitor cells (NPCs) is governed by BMP, FGF and WNT signalling. Mechanisms underlying cross-talk between these pathways at the molecular level are largely unknown.

Investigators delineate the pathway through which the proliferative BMP7 signal is transduced in NPCs in the mouse. BMP7 activates the MAPKs TAK1 and JNK to phosphorylate the transcription factor JUN, which in turn governs transcription of AP-1-element containing G1-phase cell cycle regulators such as Myc and Ccnd1 to promote NPC proliferation.

Conditional inactivation of Tak1 or Jun in cap mesenchyme causes identical phenotypes characterized by premature depletion of NPCs.

While JUN is regulated by BMP7, authors find that its partner FOS is regulated by FGF9. They demonstrate that BMP7 and FGF9 coordinately regulate AP-1 transcription to promote G1-S cell cycle progression and NPC proliferation.

These findings identify a molecular mechanism explaining the important cooperation between two major NPC self-renewal pathways.

http://www.nature.com/ncomms/2015/151204/ncomms10027/full/ncomms10027.html
 
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