Disease relevance of BMP4

• 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 BMP4

• Moreover, BMP4 is downstream to Activin signals and controls Fgf8 [3].
• SHH and BMP4 proteins negatively regulate each other's transcription, resulting in a strict complementarity between these two gene patterns on each side of the node [3].
• Thus, early BMP4 signaling coordinates left and right pathways in Hensen's node [3].
• BMP4 plays a key role in left-right patterning in chick embryos by maintaining Sonic Hedgehog asymmetry [3].
• To test our hypothesis we implanted beads soaked in recombinant BMP5 or BMP4 into the neural tube of the chicken forebrain [4].

Biological context of BMP4

• The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup [5].
• In contrast, an upregulation of PNA-binding sites and a downregulation of Bmp4 appear to be associated with this nerve deficit [6].
• We found a progressive, lateral expression of Noggin in the embryonic area, and downregulation of Msx1, a BMP4 target gene, with Msx1 expression being ultimately restricted to the most distal embryonic and extra-embryonic somatopleural mesoderm [7].
• 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 [8].

Anatomical context of BMP4

• During prestreak and gastrula stages, exposure of epiblast cells to BMP4 activity in vitro was sufficient to block the acquisition of neural fate and to promote the generation of epidermal cells [9].
• These results suggest that BMP4 and possibly other BMPs are required for multiple phases of inner ear development [10].
• Exogenous BMP4 reversed the effect of ectoderm removal on cutaneous nerve formation, but did not act as a chemoattractant [6].
• The contributions of BMP4, positive guidance cues, and repulsive molecules to cutaneous nerve formation in the chick hindlimb [6].
• BMP4 mRNA is expressed in the adjacent mesenchyme at both sides [11].

Associations of BMP4 with chemical compounds

• Retinoic acid-dependent regulation of BMP4 and Tbx5 in the embryonic chick retina [12].
• BMP-4 and -7 reversed the inhibitory effects of transforming growth factor (TGF)-alpha on basal and gonadotropin-stimulated G cell progesterone production, with greater effect in the F1 than in the F3/4 [13].
• The experiments consisted of local administration of TGF beta-1, TGF beta-2 or BMP-4 by means of heparin or Affi-gel blue beads to the chick limb autopod in the stages preceding the onset of interdigital cell death [14].

Regulatory relationships of BMP4

• We also demonstrate that islet-1 becomes up-regulated in the presumptive sensory epithelia of the inner ear in regions that are defined by the expression domains of BMP4 [15].
• Expression of bone morphogenetic protein-2 and 4--7 was detected within the growth plate, and PTHrP inhibited the expression of bone morphogenetic protein-4 and 6 [16].

Other interactions of BMP4

• Furthermore, neither BMP-4 nor BMP-7 interfere with neural induction when misexpressed in the presumptive neural plate before or after primitive streak formation [17].
• We have investigated the role of Bone Morphogenetic Protein 4 (BMP-4) and a BMP antagonist, chordin, in primitive streak formation and neural induction in amniote embryos [17].
• In order to search for signaling factors involved in PE development, we studied Bmp2 and Bmp4 expression [18].
• These signals include Bmp4, Shh and Wnt1/Wnt3a itself [19].
• In this report, we show that BMP4 (bone morphogenetic protein), a secreted protein of the TGF-beta gene family, is the earliest sensory marker identified to date for the chick inner ear [20].

Analytical, diagnostic and therapeutic context of BMP4

• In situ hybridization of BMP-4 mRNA resolved to centers at R3 and R5 but Msx-2 resolved to the R2/3 border with only a faint smear from R5 to R6 [21].

References