Disease relevance of BMP2

• To investigate the function of BMP-2 and BMP-4 during limb pattern formation, the dominant negative form of BMP receptor was overexpressed in chick leg bud via a replication-competent retrovirus to block the endogenous BMP-2/-4 signaling pathway [1].
• To better define the molecular mechanisms of induction of chondrocyte hypertrophy by BMPs, we examined the effect of BMPs on type X collagen production by 15-day chick embryo sternal chondrocytes cultured under SF conditions in the presence or absence of 30 ng/ml BMP-2, BMP-4, or BMP-7 [2].

High impact information on BMP2

• An integrated model of feather morphogenesis and evolution suggests that plumulaceous feather structure evolved by the establishment of activator-inhibitor interactions between Shh and Bmp2 signaling in the basal epithelium of the feather germ [3].
• Here, we describe the interactions between Sonic hedgehog (Shh) and bone morphogenetic protein 2 (Bmp2) signaling during feather barb ridge morphogenesis [3].
• Empirical tests support the assumptions of the model that, within the feather ectoderm, Shh (activator) up-regulates its own transcription and that of Bmp2 (inhibitor), whereas Bmp2 signaling down-regulates Shh expression [3].
• Ectopic application of BMP2, Nodal, and Car as well as combinations of this signaling molecules to the right lateral plate mesoderm revealed that BMP2 and Car need to synergize in order to specify left identity [4].
• BMP2 is a positive regulator of Nodal signaling during left-right axis formation in the chicken embryo [4].

Biological context of BMP2

• Careful titration experiments with exogenously added BMP2 or Noggin revealed that PE-specific marker gene expression depends on a low level of BMP signaling [5].
• Implantation of BMP2-secreting cells or beads filled with Noggin protein into the right sinus horn of HH stage 11 embryos resulted in downregulation of Tbx18 expression, corresponding to the results of the explant assay [5].
• These results suggest that BMP-2 and BMP-4 are the apoptotic signal molecules of the programmed cell death process in the chick limb buds [1].
• These data provide insights into how BMP-2 and BMP-4 may model and control the growth of skeletal elements during normal embryonic development, suggesting roles for both molecules in recruiting non-chondrogenic precursors to chondrogenic fate [6].
• Forced expression of Fgf10 in the femoral skin suppressed expression of Shh and a zinc finger gene snail-related (cSnR), while induced expression of Bmp2 in the interbud region, resulting in thickening of the epidermal layer [7].

Anatomical context of BMP2

• During recruitment of mesodermal cells to the outflow tract myocardium (HH10-23), BMP2, -4, -5, and -7 mRNA are expressed in the distal myocardial border and the flanking mesenchyme [8].
• During delamination of the valves, BMP4 and -6 mRNA are expressed at the ventricular side of the forming mitral valve, BMP4 mRNA at the ventricular side of the forming tricuspid valve, and BMP2, -4, and -6 mRNA at the vascular side of the forming semilunar valves [8].
• At the venous pole, BMP2, -5, and -7 mRNA are expressed in the distal myocardial border of the caval vein, while BMP2, -5, -6, and -7 mRNA are expressed in the distal myocardium around the pulmonary vein [8].
• Lithium treatments performed during early or medium streak stages cause excessive development of the anterior primitive streak, node and notochord, and lead to a degeneration of prospective ventral and posterior structures, as shown by the expression of the molecular markers GSC, CNOT1, BMP2 and Ch-Tbx6L [9].
• We have previously reported that BMP-2 markedly stimulates type X collagen expression in prehypertrophic chick sternal chondrocytes, and that type X collagen mRNA levels in chondrocytes cultured under serum-free (SF) conditions are elevated 3- to 5-fold within 24 h [2].

Associations of BMP2 with chemical compounds

• In Experiment 1, blastodermal cells cultured on a feeder layer of SIM mouse embryo-derived thioguanine and ouabain resistant (STO) cells were treated with different doses of BMP-2 and/or BMP-4, and the anti-SSEA-1 antibody reactivity of cultured cells was examined 48 h later [10].

Regulatory relationships of BMP2

• These results suggested that HOXA-13 expression in the posterior muscle masses is activated by the posteriorizing signal from the posterior mesenchyme via BMP-2 [11].

Other interactions of BMP2

• During the early developmental stages, BMP-2 and BMP-7 are expressed in the posterior distal mesenchyme leaving a less prominent expression anteriorly [12].
• The myocardial protrusions formed in the mesenchymal proximal outlet septum express BMP4, -5, and -7 mRNA, while BMP2 and -6 mRNA are expressed in the mesenchyme [8].
• After completion, BMP2 and -4 mRNA become restricted to the mesenchyme and BMP5 and -7 mRNA to the myocardium [8].
• Bmp2 expression was also not detected in mutant limb mesoderm, consistent with the hypothesis that SHH induces its expression [13].
• On the contrary, the expression of HOXA-13 in the autopodal mesenchyme was affected by neither BMP-2 nor NOGGIN/CHORDIN [11].

Analytical, diagnostic and therapeutic context of BMP2

• As a first approach to identify which BMP may be involved in myocardium formation in intra- and extracardiac mesenchyme in vivo, a survey of the expression patterns of BMP2, -4, -5, -6, and -7 mRNA is prepared by in situ hybridization in chicken embryonic hearts from HH5 to 44 [8].
• The expression of the mRNA for BMP-2, -4, -6, -7, and BMPR-IA, -IB, and -II was determined and quantified by a semiquantitative RT-PCR [14].

References