Wednesday, March 18, 2009


c-Jun is upregulated by LSJL.

c-Jun is required for the specification of joint cell fates.

"c-Jun [is] a candidate transcription factor activating [the] Wnt9a enhancer element. c-Jun is specifically expressed in joints during embryonic joint development, and its conditional deletion from early limb bud mesenchyme in mice severely affects both initiation and subsequent differentiation of all limb joints. c-Jun directly regulates Wnt16 as well as Wnt9a during early stages of joint development, causing a decrease of canonical Wnt activity in the joint interzone. Postnatally, c-Jun-deficient mice show a range of joint abnormalities, including cartilaginous continuities between juxtaposed skeletal elements, irregular articular surfaces, and hypoplasia of ligaments."

"Wnt9a misexpression can induce expression of a wide range of joint markers, including Gdf5, Autotaxin, and Chordin, in chondrogenic regions"

"gain of function of Gdf5 does not result in joint formation in the developing limb "

"verexpression of c-Jun enhanced endogenous Wnt9a expression, whereas that of a truncated form of c-Jun, which lacks its N-terminal transactivation domain (c-Jun ΔN, also known as Tam67), suppressed the Wnt9a expression "

Figure 4.
"Deletion of c-Jun from early mesenchyme causes cartilaginous continuity between juxtaposed skeletal elements. (A) Alcian blue staining on sections of interphalangeal joints in c-Jun mutants and control mice (E14.5 and E16.5). A red arrowhead indicates a joint interzone, characterized by condensed localized cells in control mice. Bars, 100 μm. (B) Skeletal staining of interphalangeal and knee joints of c-Jun mutants and control mice at P0. Red arrowheads indicate the absence of Alcian blue staining at joint spaces in control mice. Bars, 500 μm. (C) Alcian blue staining on sections of the knee joints of c-Jun mutants and control mice at E16.5 and P0. Intercondylar space and articulation between femoral condyle and tibial plateau are shown separately. Green arrows show cruciate ligaments in control mice, which are not visible in c-Jun mutants. Boxed areas are magnified on the right. Green lines on the side indicate a joint cavity space where ligaments normally arise. A solid red arrowhead shows articular cartilage layer at E16.5, characterized by condensed cell layers with a decrease in Alcian blue staining. The layer is more evident at P0 (open red arrowhead). A blue line indicates cartilage condensation in the tibia. Bars, 100 μm. "

So C-Jun KO can results in ectopic chondrogenesis but probably not height due to the dysregulation caused.

"JunB, JunD, Fra2, and Atf2 are weakly expressed in developing joints and were also found at a comparable level in the surrounding perichondrium, while other AP1 family molecules (c-Fos, FosB, and Fra1) were not detectable in developing joints"

"We found a dramatically decreased level of Axin2, a classical Wnt canonical target, in the developing joints of c-Jun mutants."

"-Jun mutants show the abnormal formation of joint interzone molecularly and morphologically, including failure to express several interzone-specific genes, such as Autotaxin and Chordin"

No comments:

Post a Comment