Figure 3: Prox1 regulates the slow muscle fibre gene program in skeletal muscle.

(a) MyHC I (Myh7) expression in muscle fibres (arrows) in AAV8-Prox1 and AAV8-Ctrl transduced TA muscle. (b) Expression of myosin heavy chain and calcium-signalling genes in AAV8-Prox1 and AAV8-Ctrl transduced TA muscle. Note that the expression of slow fibre -specific genes are upregulated and fast MyHC genes downregulated in Prox1 overexpressing muscles. (c) Heat map from GSEA analysis showing that Prox1 overexpression in TA muscle leads to expression of many soleus specific myofibrillar genes (red colour indicates positive and blue negative enrichment). (d) Effect of Prox1 deletion on soleus muscle gene expression (HSA-Cre^ERT2;Prox1^fl/fl mice). Note the increased expression of fast MyHCs Myh2 and Myh4 RNAs, whereas slow troponin isoform RNAs and Myh7 RNA are decreased. (e) Deletion of Prox1 in slow soleus muscle with AAV-Cre leads to marked downregulation of MyHC I protein. Data is presented as mean±s.e.m., n=5+5 in a,b, n=3+3 in c, n=4+4 in d,e. Student’s two-tailed unpaired t-test, *P<0.05, **P<0.01, ***P<0.001. Both overexpression and deletion experiments were conducted two times on independent mouse cohorts. WT, wild-type. Scale bars, 50 μm.