Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis.
ABSTRACT The murine dominant negative helix-loop-helix (dnHLH) proteins inhibit the activities of bHLH transcription factors in diverse cell lineages (Benezra et al.  Cell 61:49-59; Christy et al  Proc. Natl. Acad. Sci. U.S.A. 88:1815-1819; Sun et al  Mol. Cell Biol. 11: 5603-5611; Riechmann et al.  Nucleic Acids Res. 22:749-755). Currently, there are four members in the dnHLH family, Id1, Id2, Id3, and Id4. In this report, we have performed a detailed comparative in situ hybridization analysis to examine their expression pattern during post-gastrulational mouse development. Id1, 2, and 3 are expressed in multiple tissues, whereas Id4 expression can only be detected in neuronal tissues and in the ventral portion of the epithelium of the developing stomach. The regions where Id1-3 genes are expressed, such as gut, lung, kidney, tooth, whisker, and several glandular structures, are undergoing active morphogenetic activities. The expression patterns of Id1, 2, and 3 overlap in many organs, except in the tissue derived from primitive gut. In the latter, Id1 and Id3 signals are detected in the mesenchyme surrounding the epithelium, whereas Id2 is expressed within the epithelium. The difference in the patterns of expressions of Id2-3 and Id4 suggest that the dominant negative transcriptional activity of these two subclasses of the Id family may have different physiological consequences.
Article: Identification and expression profile of the ID gene family in the rainbow trout (Oncorhynchus mykiss).[show abstract] [hide abstract]
ABSTRACT: ID proteins are negative regulators of basic helix-loop-helix transcription factors governing growth and development in mammals. However, little is known about the ID gene function and expression in fish. We report the identification and characterization of two new rainbow trout ID genes (ID1D and ID2B) and extend our expression analyses of two previously identified ID genes (ID1A and ID2A). Phylogenetic analyses indicate an evolutionary relationship between ID1A and ID1D and between ID1B and ID1C, suggesting a mechanism of divergence throughout salmonid evolution. To access the expression of these genes in adult and developing fish, we measured the relative transcript abundance of four ID1 and two ID2 genes by real-time PCR. ID1 transcripts were expressed in a variety of tissues and the ID1 paralogues showed similar patterns of expression, whereas the ID2 paralogues were differentially expressed. To access the role of the ID genes during embryonic development, gene expression was measured at early (day 0 and day 2), mid (day 9 and day 18) and late (day 30 and day 50) embryonic development. ID1A and ID1D expression remained unchanged throughout embryonic development, while ID1B and ID1C were lowest during early, highest at mid, and decreased during late embryonic development. The ID2 transcripts revealed the highest expression in unfertilized eggs and day 2 embryos, and remained low throughout the remainder of embryonic development. The sequence analyses and gene expression patterns implicate gene and genome duplication in rainbow trout ID gene evolution and suggest an extensive role for the IDs in rainbow trout growth and development.Biochimica et Biophysica Acta 06/2005; 1729(1):64-73. · 4.66 Impact Factor
Article: Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells.[show abstract] [hide abstract]
ABSTRACT: ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication. Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.BMC Cell Biology 01/2010; 11:2. · 2.59 Impact Factor
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ABSTRACT: The inhibitor of differentiation Id2 is a target of the retinoblastoma (Rb) protein during mouse embryogenesis. In Rb(+/-) mice, LOH at the wild-type Rb allele initiates pituitary adenocarcinoma, a tumor derived from embryonic melanotropes. Here we identify a critical role for Id2 in initiation, growth, and angiogenesis of pituitary tumors from Rb(+/-) mice. We show that proliferation and differentiation are intimately coupled in Rb(+/-) pituitary cells before tumor initiation. In Id2-null pituitaries, premature activation of basic helix-loop-helix-mediated transcription and expression of the cdk inhibitor p27(Kip1) impairs the proliferation of melanotropes and tumor initiation. Without Id2, Rb(+/-) mice have fewer early tumor lesions and a markedly decreased proliferation rate of the tumor foci. Expression of Id2 by pituitary tumor cells promotes growth and angiogenesis by functioning as a master regulator of vascular endothelial growth factor (VEGF). In human neuroblastoma, the N-Myc-driven expression of Id2 is sufficient and necessary for expression of VEGF. These results establish that aberrant Id2 activity directs initiation and progression of embryonal cancer.Molecular and Cellular Biology 06/2005; 25(9):3563-74. · 5.53 Impact Factor