High impact information on bmp4

• Our findings indicate that Mix.1 participates in a BMP-4 signalling pathway to pattern ventral mesoderm, and suggest a model whereby dimerization of homeodomain proteins regulates dorsal-ventral patterning [1].
• Ectopic expression of alpha1-PDX phenocopies the effect of blocking endogenous BMP activity, leading to dorsalization of mesoderm and direct neural induction. alpha1-PDX-mediated neural induction can be reversed by co-expression of downstream components of the BMP-4 signaling pathway [2].
• These studies provide the first in vivo evidence that furin and/or PC6 proteolytically activate BMP-4 during vertebrate embryogenesis [2].
• Ectopic expression of the ventralizing morphogen BMP-4 (bone morphogenetic protein-4) in the dorsal lip (Spemann organizer) of Xenopus embryos blocks transcription of dorsal-lip-specific early response genes [3].
• Consistent with this hypothesis, alpha1-PDX prevents cleavage of BMP-4 in an oocyte translation assay [2].

Biological context of bmp4

• Finally, we show that while radar-injected swirl embryos still exhibit a strongly dorsalized phenotype, the overexpression of Radar into swirl/bmp2b mutant embryos restores ventral marker expression, including bmp4 expression [4].
• BMP-4 is synthesized as an inactive precursor that is proteolytically activated by cleavage following the amino acid motif -Arg-Ser-Lys-Arg-. Very little is known about processing and secretion of BMPs [2].
• These results suggest that BMP-4 requires mesoderm induction to generate a program of gene expression, which regulates the specification of hematopoietic mesoderm by GATA factors [5].
• Xenopus msx1 mediates epidermal induction and neural inhibition by BMP4 [6].
• Consistent with the BMP-4 inductive nature of this region, this element exhibits transcriptional activation upon ectopic expression of Smad1 and Smad4 [7].

Anatomical context of bmp4

• At tailbud stages BMP-4 is expressed in the spinal cord roof plate, neural crest, eye and auditory vesicle [8].
• PV.1 is inducible in uncommited ectoderm by the ventralizing growth factor BMP4 and counteracts the dorsalizing effects of the dominant negative BMP4 receptor [9].
• When high doses of BMP-4 were used in this explant assay, few erythroid cells were detected [5].
• Injection of BMP-4 RNA, but not activin RNA, induced Xmsx-1 expression in the dorsal marginal zone at the early gastrula stage (stage 10+), and introduction of a dominant negative form of BMP-4 receptor RNA suppressed Xmsx-1 expression in animal cap and ventral marginal zone explants at stage 14 [10].
• The effect of an extremely small dose of poly(A)+ RNA on erythroid differentiation suggests that in addition to XBMP-4 there exist substances, expressed later than st.7 in the animal pole region, which can stimulate erythrocyte differentiation in the ventral mesoderm [11].

Associations of bmp4 with chemical compounds

• In embryos ventralized by UV irradiation and suramin treatment, BMP-4 zygotic transcripts accumulate prematurely and the entire marginal zone expresses this gene [8].
• In addition, we found that the connective tissue-specific expression of BMP-4 mRNA is up-regulated by sonic hedgehog (Shh), whose epithelium-specific expression is directly induced by TH [12].

Analytical, diagnostic and therapeutic context of bmp4

• Electrophoretic mobility shift assays with total cellular extracts demonstrated that a DNA fragment encompassing this region was competent in the formation of a BMP-4-induced protein-DNA complex containing Smad1 [7].
• Northern-blot analysis showed that the latter vector was more efficient for Xenopus BMP-4 expression [13].
• More importantly, using organ culture and immunohistochemical procedures, we have shown that BMP-4 not only represses cell proliferation of the connective tissue but promotes differentiation of the intestinal absorptive epithelium [12].
• Our reverse transcriptase-polymerase chain reaction and in situ hybridization analyses indicated that mRNA of BMPR-IA, a type I receptor of BMP-4, is expressed in both the developing connective tissue and progenitor cells of the adult epithelium [12].
• To clarify possible roles of BMP-4 in intestinal remodeling during metamorphosis, we have examined its expression in X. laevis intestine by using in situ hybridization and organ culture techniques [14].

References