Dual function of VGLL4 in muscle regeneration

다국어 초록 (Multilingual Abstract)

VGLL4 has previously been identified as a negative regulator of YAP. Here we show that VGLL4 regulates muscle regeneration in both YAP‐dependent and YAP‐independent manners at different stages. Knockout of VGLL4 in mice leads to smaller myofiber size and defective muscle contraction force. Furthermore, our studies reveal that knockout of VGLL4 results in increased muscle satellite cells proliferation and impaired myoblast differentiation, which ultimately leads to delayed muscle regeneration. Mechanistically, the results show that VGLL4 works as a conventional repressor of YAP at the proliferation stage of muscle regeneration. At the differentiation stage, VGLL4 acts as a co‐activator of TEAD4 to promote MyoG transactivation and facilitate the initiation of differentiation in a YAP‐independent manner. Moreover, VGLL4 stabilizes the protein–protein interactions between MyoD and TEAD4 to achieve efficient MyoG transactivation. Our findings define the dual roles of VGLL4 in regulating muscle regeneration at different stages and may open novel therapeutic perspectives for muscle regeneration.










VGLL4 has previously defined as a negative regulator of YAP. This study reveals that VGLL4 exhibits opposing effects on TEAD4 mediated transcription in YAP dependent and independent manners at different stages of muscle regeneration, thereby striking a balance between muscle stem cell proliferation and differentiation.



Global VGLL4 knockout mice exhibit enhanced myoblast proliferation, which is reversed by muscle satellite cell specific YAP depletion.

Muscle stem cell specific VGLL4 knockout mice display impaired muscle differentiation.

At the proliferation stage of muscle regeneration, VGLL4 inhibits YAP and restricts muscle satellite cell differentiation.

At the differentiation stage of muscle regeneration, VGLL4 acts as a co‐activator of MyoD to promote MyoG transactivation in a YAP independent manner.


Analyses on knockout mice reveal that VGLL4 exhibits opposing effects on TEAD4 mediated transcription in different stages of muscle regeneration, thereby striking a balance between muscle stem cell proliferation and differentiation.