بيان ونقش BMP3 در طي رشد اندام جوجه
استاد: خانم دكتر محمودي
دانشجو:فهيمه شعبانلو
دوره كارشناسي ارشد رشته علوم جانوري
Bone morphogenetic proteins (BMPs), members of the transforming growth factor- superfamily of structurally related secreted growth factors, are expressed throughout the developing skeleton where they influence cell type specification, cell differentiation, and apoptosis during endochondral ossification. In the skeleton, the primary way BMPs affect their target cells is by binding to receptor complexes consisting of combinations of type I (Alk2, Alk3, or Alk6) and type II (BMPR-II or ActRIIA, ActRIIB) serine-threonine kinases that then activate the canonical BMP-specific Smad signaling pathway (R-Smads 1,5,8), or the MAPK pathway (Derynck and Zhang,[2003]). As BMP receptors are present in various combinations on virtually all skeletal cell types, BMP activity must be tightly regulated both spatially and temporally to ensure proper bone development (Canalis et al.,[2003]).
One way in which precise control of BMP signals occurs is through the formation of BMP ligand and antagonist complexes that prevent BMPs from engaging their receptors
Antagonists are secreted into the extracellular space where they bind with high affinity to BMPs, and dampen BMP signaling (Balemans and Van Hul,[2002])
Another level of control of BMP activity in the skeleton appears to come from BMP3, The net result of the BMP3-ActRIIB interaction is a decrease in BMP
We find that misexpression of BMP3 in the chick limb reduces BMP signaling, enhancing chondrocyte proliferation before hypertrophic chondrocyte differentiation, thus widening skeletal elements and producing joint fusions.
Expression of BMP3 during normal chick limb development. A-L: Whole-mount in situ hybridization of BMP3 expression in developing chick legs (A-G) A: At stage 20, BMP3 is expressed in the developing somites but not in the hindlimb bud. B: At stage 23, BMP3 is expressed in the dorsal and ventral mesenchyme. C: At stage 24, BMP3 expression broadens and expands distally. D: Anterior view of stage 24 leg bud. BMP3 transcripts are excluded from the central core mesenchyme. E: At stage 25, BMP3 is expressed in both the proximal and distal mesenchyme. F: At stage 27, BMP3 expression outlines where the future zuegopod will form. G: At stage 31, BMP3 is expressed in the perichondrium and forming bone collar of the developing bones in the leg and foot and in the digit tips. At stage 23, ActRIIB transcripts are found throughout the limb mesenchyme surrounding the developing cartilages (Fig. 2E) and appear to be expressed near BMP3 in the dorsal and ventral mesenchyme (Fig. 2A,E).
we found that overexpression of BMP3 caused an obvious expansion of the cartilages of the humerus and ulna when compared with the contralateral control (n = 28/30 with widened skeletal elements; Fig. 4A,). When we performed histological analysis of day 8 wings, we found that the cartilages of the proximal ulna and humerus were clearly wider in the BMP3-infected limb, and no joint space formed between these skeletal elements (Fig. 4D).
To determine whether misexpression of BMP3 would alter BMP signaling, we analyzed phospho-Smad 1,5,8 levels in control and RCAS-BMP3 infected limb buds 48 hr after injection (day 5). Limbs infected with RCAS-BMP3 showed reduced levels of phospho-Smad 1,5,8 when compared with controls (Fig. 3B).
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