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J Biol Chem, Vol. 274, Issue 28, 19838-19845, July 9, 1999
From the Bone morphogenetic proteins
(BMPs) are morphogenetic signaling molecules
essential for embryonic patterning. To obtain molecular insight into
the influence of BMPs on morphogenesis, we searched for new genes
directly activated by BMP signaling. In vitro cultured mouse embryonic stem (ES) cells were used, cultivated in chemically defined growth medium (CDM). CDM-cultured ES cells responded very selectively to stimulation by various mesoderm inducers (BMP2/4, activin A, and basic fibroblast growth factor). BMP2/4 rapidly induced
transcript levels of the homeobox genes Msx-1 and
Msx-2 and the proto-oncogene JunB, whereas
c-jun transcripts displayed delayed albeit prolonged
increase. Using differential display cDNA cloning, six direct BMP
target genes were identified. These include Id3, which
showed strong mRNA induction, and the moderately induced
Cyr61, DEK, and eIF4AII genes, as
well as a gene encoding a GC-binding protein. Besides Id3,
also the Id1 and Id2 genes were activated by
BMP4 in both ES cells and a range of different cell lines.
Id genes encode negative regulators of basic
helix-loop-helix transcription factors. In vivo we observed
local ectopic expression of Id3 and Msx-2
mRNAs in Ft/+ embryos at overlapping regions of ectopic
Bmp4 misexpression. We therefore propose that the
Msx and Id genes are direct target genes of
embryonic BMP4 signaling in vivo.
Id Genes Are Direct Targets of Bone Morphogenetic
Protein Induction in Embryonic Stem Cells
,,,, and**
Institut für Molekularbiologie,
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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Z.-J. Shen, T. Nakamoto, K. Tsuji, A. Nifuji, K. Miyazono, T. Komori, H. Hirai, and M. Noda Negative Regulation of Bone Morphogenetic Protein/Smad Signaling by Cas-interacting Zinc Finger Protein in Osteoblasts J. Biol. Chem., August 9, 2002; 277(33): 29840 - 29846. [Abstract] [Full Text] [PDF]
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D. P. Tan, K. Nonaka, G. H. Nuckolls, Y. H. Liu, R. E. Maxson, H. C. Slavkin, and L. Shum YY1 activates Msx2 gene independent of bone morphogenetic protein signaling Nucleic Acids Res., March 1, 2002; 30(5): 1213 - 1223. [Abstract] [Full Text] [PDF]
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T. Lopez-Rovira, E. Chalaux, J. Massague, J. L. Rosa, and F. Ventura Direct Binding of Smad1 and Smad4 to Two Distinct Motifs Mediates Bone Morphogenetic Protein-specific Transcriptional Activation of Id1 Gene J. Biol. Chem., January 25, 2002; 277(5): 3176 - 3185. [Abstract] [Full Text] [PDF]
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O. Rozenblatt-Rosen, E. Mosonego-Ornan, E. Sadot, L. Madar-Shapiro, Y. Sheinin, D. Ginsberg, and A. Yayon Induction of chondrocyte growth arrest by FGF: transcriptional and cytoskeletal alterations J. Cell Sci., January 2, 2002; 115(3): 553 - 562. [Abstract] [Full Text] [PDF]
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A. E. Kearns, M. M. Donohue, B. Sanyal, and M. B. Demay Cloning and Characterization of a Novel Protein Kinase That Impairs Osteoblast Differentiation in Vitro J. Biol. Chem., November 2, 2001; 276(45): 42213 - 42218. [Abstract] [Full Text] [PDF]
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M. E. Bahamonde and K. M Lyons BMP3: To Be or Not To Be a BMP J. Bone Joint Surg. Am., April 1, 2001; 83(90010): S56 - 62. [Abstract] [Full Text] [PDF]
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M. E. Bahamonde and K. M Lyons BMP3: To Be or Not To Be a BMP J. Bone Joint Surg. Am., March 1, 2001; 83(1_suppl_1): S56 - S62. [Abstract] [Full Text] [PDF]
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M. Schuldiner, O. Yanuka, J. Itskovitz-Eldor, D. A. Melton, and N. Benvenisty From the Cover: Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells PNAS, October 10, 2000; 97(21): 11307 - 11312. [Abstract] [Full Text] [PDF]
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