Abstract
ABSTRACT The transcription factor family NF-κB/Rel is responsible for the regulation of a large number of cellular genes and some viruses. Since there is a strong similarity between the NF-κB/Rel family members and the Drosophila melanogaster protein DORSAL, which is activated early during embryogenesis, we were interested in determining the pattern of NF-κB activity during mouse development. Two lacZ reporter constructs, each driven by promoter elements that are dependent on the presence of nuclear NF-κB/Rel activity, were used to produce transgenic mice. The analysis of these mice did not identify nuclear NF-κB/Rel activity in early development prior to implantation or during the gastrulation processes. Earliest expression of the lacZ transgene was detected on day E12.5. Before birth lacZ expression was seen in discrete regions of the rhombencephalon of the developing brain, in the spinal medulla, in some of the blood vessels and in the thymus. After birth, the NF-κB/Rel activity in the thymus remained but nuclear activity was also found in the bone marrow, in the spleen and in the capsule of the lymph nodes. In the central nervous system, drastic changes in NF-κB/Rel activity could be observed in the first 3 weeks after birth, when the cortex and the cerebellum reach functional and morphological maturity. Considering the results of the p50, p65, relB and c-rel knock-out mice and our present findings, we believe that the NF-κB/Rel proteins known so far are probably not implicated in processes of early development and differentiation of the different tissues, but rather in maintaining their function once matured.
References
41
Referenced
189
10.1146/annurev.iy.12.040194.001041/ Annu. Rev. Immunol / Function and activation of NF-κB in the immune system by Baeuerle (1994)10.1016/0169-328X(93)90119-A/ Mol. Brain Res / NF-κB-like factors in the murine brain. Developmentally-regulated and tissue-specific expression by Bakalkin (1993)10.1101/gad.7.11.2064/ Genes Dev / The I-κB proteins : multifunctional regulators of rel/NF-κB transcription factors by Beg (1993)10.1038/376167a0/ Nature / Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB by Beg (1995)10.1016/0968-0004(92)90321-Y/ Trends Biochem Sci / NF-κB and related proteins: Rel/dorsal homologies meet ankyrin-like repeats by Blank (1992)10.1242/dev.118.4.1221/ Development / Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells by Carrasco (1993)10.1242/dev.120.10.2991/ Development / Developmental expression of the mouse c-rel proto-oncogene in hematopoietic organs by Carrasco (1994)10.1073/pnas.81.7.1991/ Proc. Natl. Acad. Sci. USA / Genomic sequencing by Church (1984)10.4049/jimmunol.150.7.2794/ J. Immunol / Promoter of the human NF-κB p50/p105 gene : regulation by NF-κB subunits and by c-Rel by Cogswell (1993)10.1016/S0021-9258(18)43831-8/ J. Biol. Chem / Rapid activation of post-hepatectomy factor/nuclear factor κB in hepatocytes, a primary response in the regenerating liver by Cressman (1994)10.1016/S0074-7696(08)61873-2/ Int. Rev. Cytol / NF-κB and rel: participants in a multiform transcriptional regulatory system by Grilli (1993)10.1073/pnas.92.20.9077/ Proc. Natl. Acad. Sci. USA / Synaptic activation of NF-κB by glutamate in cerebellar granule neurons in vitro by Guerrini (1995){'key': '2025021323025207000_DEVELOP_122_7_2117C13', 'first-page': '56', 'article-title': 'Transgene detection in unpurified mouse tail DNA by polymerase chain reaction', 'volume': '10', 'author': 'Hanley', 'year': '1991', 'journal-title': 'BioTechniques'}/ BioTechniques / Transgene detection in unpurified mouse tail DNA by polymerase chain reaction by Hanley (1991){'volume-title': 'Manipulating the Mouse Embryo. A Laboratory Manual', 'year': '1994', 'author': 'Hogan', 'key': '2025021323025207000_DEVELOP_122_7_2117C14'}/ Manipulating the Mouse Embryo. A Laboratory Manual by Hogan (1994)10.1016/S0021-9258(18)42004-2/ J. Biol. Chem / Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1) by Iademarco (1992)10.1016/0925-4773(93)90031-R/ Mech. Dev / Brain synapses contain inducible forms of the transcription factor NF-κB by Kaltschmidt (1993){'key': '2025021323025207000_DEVELOP_122_7_2117C17', 'first-page': '39813992', 'article-title': 'Constitutive NF-κB activity in neurons', 'volume': '14', 'author': 'Kaltschmidt', 'year': '1994', 'journal-title': 'Mol. Cell. Biol'}/ Mol. Cell. Biol / Constitutive NF-κB activity in neurons by Kaltschmidt (1994){'key': '2025021323025207000_DEVELOP_122_7_2117C18', 'first-page': '7180', 'article-title': 'Cyclic AMP-independent ATF family members interact with NF-κB and function in the activation of the E-selectin promoter response to cytokines', 'volume': '13', 'author': 'Kaszubska', 'year': '1993', 'journal-title': 'Mol. Cell. Biol'}/ Mol. Cell. Biol / Cyclic AMP-independent ATF family members interact with NF-κB and function in the activation of the E-selectin promoter response to cytokines by Kaszubska (1993)10.1101/gad.9.16.1965/ Genes Dev / Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity and interleukin-2 expression by Köntgen (1995)10.1016/0896-6273(89)90266-3/ Neuron / A brainspecific transcription activator by Korner (1989)10.1242/dev.117.1.97/ Development / Changing patterns of gene expression define 4 stages of cerebellar granule neuron differentiation by Kuhar (1993)10.1093/nar/19.15.4293/ Nucleic Acids Res / Simplified mammalian DNA isolation procedure by Laird (1991)10.1038/365767a0/ Nature / Distinct NF-κB/Rel transcription factors are responsible for tissue-specific and inducible gene activation by Lernbecher (1993){'key': '2025021323025207000_DEVELOP_122_7_2117C24', 'first-page': '5349', 'article-title': 'Sequential induction of NF-κB/Rel family proteins during B-cell terminal differentiation', 'volume': '14', 'author': 'Liou', 'year': '1994', 'journal-title': 'Mol Cell Biol'}/ Mol Cell Biol / Sequential induction of NF-κB/Rel family proteins during B-cell terminal differentiation by Liou (1994)10.1101/gad.7.4.705/ Genes Dev / p105 and p98 precursor proteins play an active role in NF-κB-mediated signal transduction by Mercurio (1993)10.1016/S0959-437X(05)80276-X/ Curr. Opin. Genet. Dev / The inhibitory ankyrin and activator Rel proteins by Nolan (1992){'volume-title': 'In The Rat Nervous System', 'year': '1985', 'author': 'Paxinos', 'key': '2025021323025207000_DEVELOP_122_7_2117C27'}/ In The Rat Nervous System by Paxinos (1985)10.1002/j.1460-2075.1993.tb06110.x/ EMBO J / NF-κB activates the HIV promoter in neurons by Rattner (1993)10.1016/0092-8674(92)90353-E/ Cell / The precursor of NF-κB p50 has IκB-like functions by Rice (1992)10.1016/0092-8674(95)90415-8/ Cell / Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses by Sha (1995){'key': '2025021323025207000_DEVELOP_122_7_2117C31', 'first-page': '6283', 'article-title': 'Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-κB subunits in endothelial and epithelial cells', 'volume': '13', 'author': 'Shu', 'year': '1993', 'journal-title': 'Mol. Cell. Biol'}/ Mol. Cell. Biol / Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-κB subunits in endothelial and epithelial cells by Shu (1993)10.1146/annurev.cb.10.110194.002201/ Annu. Rev. Cell Biol / Structure, regulation, and function of NF-κB by Siebenlist (1994)10.1128/jvi.69.8.4593-4599.1995/ J. Virol / Longterm expression in sensory neurons in tissue culture from herpes simplex virus type 1 (HSV-1) promoters in an HSV-1-derived vector by Smith (1995)10.1126/science.3118464/ Science / Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene c-rel by Steward (1987)10.1016/0092-8674(92)90466-P/ Cell / The origin of pattern and polarity in the Drosophila embryo by St. Johnston (1992)10.1002/j.1460-2075.1992.tb05042.x/ EMBO J / The characterization of the promoter of the gene encoding the p50 subunit of NF-κB indicates that it participates in its own regulation by Ten (1992){'key': '2025021323025207000_DEVELOP_122_7_2117C37', 'first-page': '2898', 'article-title': 'Rapid induction in regenerating liver of RL/IF-1 (an IκB that inhibits NF-κB, RelB-p50, and c-rel-p50) and PHF, a novel κB site-binding complex', 'volume': '12', 'author': 'Tewari', 'year': '1992', 'journal-title': 'Mol. Cell. Biol'}/ Mol. Cell. Biol / Rapid induction in regenerating liver of RL/IF-1 (an IκB that inhibits NF-κB, RelB-p50, and c-rel-p50) and PHF, a novel κB site-binding complex by Tewari (1992)10.1016/0076-6879(93)25030-6/ Methods in Enzymology / Application of lacZ gene fusion to preimplantation development by Vernet (1993){'key': '2025021323025207000_DEVELOP_122_7_2117C39', 'first-page': '3289', 'article-title': 'Constitutive and inducible Rel/NF-κB activities in mouse thymus and spleen', 'volume': '9', 'author': 'Weih', 'year': '1994', 'journal-title': 'Oncogene'}/ Oncogene / Constitutive and inducible Rel/NF-κB activities in mouse thymus and spleen by Weih (1994)10.1016/0092-8674(95)90416-6/ Cell / Multiorgan inflammation and hemopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-κB/Rel family by Weih (1995)10.1093/nar/19.10.2645/ Nucleic Acids Res / An NF-κB-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule (ELAM) gene transcription by Whelan (1991)
Dates
| Type | When |
|---|---|
| Created | 4 years, 4 months ago (April 25, 2021, 10:40 p.m.) |
| Deposited | 6 months, 2 weeks ago (Feb. 13, 2025, 6:03 p.m.) |
| Indexed | 1 month, 3 weeks ago (July 1, 2025, 9:51 a.m.) |
| Issued | 29 years, 1 month ago (July 1, 1996) |
| Published | 29 years, 1 month ago (July 1, 1996) |
| Published Online | 29 years, 1 month ago (July 1, 1996) |
| Published Print | 29 years, 1 month ago (July 1, 1996) |
@article{Schmidt_Ullrich_1996, title={NF-κB activity in transgenic mice: developmental regulation and tissue specificity}, volume={122}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.122.7.2117}, DOI={10.1242/dev.122.7.2117}, number={7}, journal={Development}, publisher={The Company of Biologists}, author={Schmidt-Ullrich, Ruth and Mémet, Sylvie and Lilienbaum, Alain and Feuillard, Jean and Raphaël, Martine and Israël, Alain}, year={1996}, month=jul, pages={2117–2128} }