Four and a half domain 2 (FHL2) scaffolding protein is a marker of connective tissues of developing digits and regulates fibrogenic differentiation of limb mesodermal progenitors.

Summary FHL2 is a multifunctional scaffolding protein of well‐known function regulating cell signaling cascades and gene transcription in cancer tissues. However, its function in embryonic systems is poorly characterized. Here, we show that Fhl2 is involved in the differentiation of connective tissues of developing limb autopod. We show that Fhl2 exhibits spatially restricted and temporally dynamic expression around the tendons of developing digits, interphalangeal joint capsules, and fibrous peridigital tissue. Immunolabeling analysis of the skeletal progenitors identified a predominant, but not exclusive, cytoplasmic distribution of FHL2 being associated with focal adhesions and actin cytoskeleton. In the course chondrogenic differentiation of cultures of limb skeletal progenitors, the expression of Fhl2 is down‐regulated. Furthermore, cultures of skeletal progenitors overexpressing Fhl2 takes on a predominant fibrogenic appearance. Both, gain‐of‐function and loss‐of‐function experiments in the micromass culture assays revealed a positive transcriptional influence of Fhl2 in the expression of fibrogenic markers including Scleraxis, Tenomodulin, Tenascin C, βig‐h3, and Tgif1. We further show that the expression of Fhl2 is positively regulated by profibrogenic signals including Tgfβ2, all‐trans‐retinoic acid, and canonical Wnt signaling molecules, and negatively regulated by prochondrogenic factors of the BMP family. Expression of Fhl2 is also regulated ne...
Source: Journal of Tissue Engineering and Regenerative Medicine - Category: Biotechnology Authors: Tags: RESEARCH ARTICLE Source Type: research