PMID- 10391928
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 28
DP  - 1999 Jul 9
TI  - Id genes are direct targets of bone morphogenetic protein induction in embryonic 
      stem cells.
PG  - 19838-45
AB  - 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.
FAU - Hollnagel, A
AU  - Hollnagel A
AD  - Institut fur Molekularbiologie, Medizinische Hochschule Hannover, D-30625
      Hannover, Germany.
FAU - Oehlmann, V
AU  - Oehlmann V
FAU - Heymer, J
AU  - Heymer J
FAU - Ruther, U
AU  - Ruther U
FAU - Nordheim, A
AU  - Nordheim A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bmp4 protein, mouse)
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Idb1 protein, mouse)
RN  - 0 (Inhibitor of Differentiation Protein 1)
RN  - 0 (MSX1 Transcription Factor)
RN  - 0 (MSX2 protein)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 4
MH  - Bone Morphogenetic Proteins/*genetics
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics
MH  - Fibroblast Growth Factor 2/genetics
MH  - Gene Expression Regulation, Developmental
MH  - Genes, Homeobox/genetics
MH  - Helix-Loop-Helix Motifs/genetics
MH  - Homeodomain Proteins/genetics
MH  - Inhibitor of Differentiation Protein 1
MH  - MSX1 Transcription Factor
MH  - Mice
MH  - Proto-Oncogene Proteins c-jun/genetics
MH  - RNA, Messenger/metabolism
MH  - *Repressor Proteins
MH  - Signal Transduction/genetics
MH  - Stem Cells/*metabolism
MH  - Transcription Factors/*genetics
EDAT- 1999/07/03 00:00
MHDA- 1999/07/03 00:01
CRDT- 1999/07/03 00:00
PHST- 1999/07/03 00:00 [pubmed]
PHST- 1999/07/03 00:01 [medline]
PHST- 1999/07/03 00:00 [entrez]
AID - 10.1074/jbc.274.28.19838 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 9;274(28):19838-45. doi: 10.1074/jbc.274.28.19838.