Differential Pax6 promoter activity and transcript expression during forebrain development

Anderson, Tonya R.; Hedlund, Eva; Carpenter, Ellen M.

doi:10.1016/s0925-4773(02)00051-5

Cited by 29 publications

(24 citation statements)

References 8 publications

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“…Consequently, the expression of Pax6 is affected in the knock-in; however, the degree to which it is affected determines the severity of the eye phenotype. Pax6 expression is regulated by two promoters that specify tissue and developmental stage-specific expression, each of which is located upstream of the gene (Anderson et al 2002). While neither of these promoters has been shown to be dependent on NF-B, Pax6 gene expression has been shown to be regulated by an element located ∼150 kb downstream from the gene.…”

Section: Discussionmentioning

confidence: 99%

Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms

Dong¹,

Jimi²,

Zhong³

et al. 2008

Genes Dev.

126

131

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Cells from a "knock-in" mouse expressing a NF-B p65 mutant bearing an alanine instead of serine at position 276 (S276A) display a significant reduction of NF-B-dependent transcription, even though the mutant p65 forms appropriate complexes that translocate normally to the nucleus and bind to DNA. Surprisingly, however, instead of the expected embryonic lethality from hepatocyte apoptosis seen in the absence of NF-B activity, the S276A knock-in embryos die at different embryonic days due to variegated developmental abnormalities. We now demonstrate that this variegated phenotype is due to epigenetic repression resulting from the recruitment of histone deacetylases by the nonphosphorylatable form of NF-B into the vicinity of genes positioned fortuitously near NF-B-binding sites. Therefore, unphosphorylated nuclear NF-B can affect expression of genes not normally regulated by NF-B through epigenetic mechanisms.[Keywords: Epigenetics; inflammation; NF-B; gene expression; phosphorylation] Supplemental material is available at http://www.genesdev.org. The transcription factor NF-B plays a critical role in the inducible expression of genes involved in many biological processes (Baldwin 1996;Ghosh et al. 1998). In unstimulated cells, NF-B exists in the cytosol, bound to inhibitory IB proteins. Stimulation of cells leads to the activation of the IB kinase (IKK) complex, which then phosphorylates IB proteins on two N-terminal serine residues, leading to its polyubiquitination and subsequent degradation by the proteasome. The released NF-B translocates to the nucleus, binds to cognate sites in the promoters of responsive genes, and induces their expression. This cytoplasmic-to-nuclear translocation has remained a paradigm for inducible transcription factors, and it has been assumed that, once NF-B reached the nucleus, it would be capable of driving transcription. However, recent studies have begun to suggest that such a model might be too simplistic and may fail to account for the complexity that underlies the process of NF-B activation (Chen and Greene 2004;Hayden and Ghosh 2004;Vermeulen et al. 2006).A hint that the transcriptional activity of NF-B requires additional regulatory steps first came from biochemical studies where the catalytic subunit of cAMPdependent protein kinase (PKAc) was found to copurify with cytosolic NF-B:IB complexes (Zhong et al. 1997). Subsequent analysis indicated that in response to specific stimuli PKAc phosphorylates the p65 NF-B subunit at a consensus PKA phosphorylation site located within the Rel homology domain. Overexpression experiments suggested that mutation of this serine residue at position 276 to alanine (S276A) abolishes the ability of the transfected p65 protein to drive transcription, even though the mutant protein can assemble into complexes with other Rel proteins and IBs and bind normally to DNA (Zhong et al. 1997(Zhong et al. , 1998. Further studies showed that phosphorylation of p65 at Ser 276 allows efficient recruitment of the coactivator CREB-binding protein (CBP)/p300 a...

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Section: Discussionmentioning

confidence: 99%

Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms

Dong¹,

Jimi²,

Zhong³

et al. 2008

Genes Dev.

126

131

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“…Buds collected from three embryos of the same genotype were pooled and total RNA was extracted using RNA Wiz as described (Anderson et al, 2002), reverse transcribed using Superscript II (Invitrogen, Carlsbad, CA, USA), then amplified using the following primers: ApoER2 forward, 5Ј-AGCGTTTGTACTGGGTG-GAC-3Ј; ApoER2 reverse, 5Ј-GCTGGAGATTTGAGGAGCAG-3Ј; VLDLR forward, 5Ј-ACGGCCAGTGTGTTCCTAAC-3Ј; VLDLR reverse, 5Ј-CCATCGTCACAGTCATCCTG-3Ј.…”

Section: Rt-pcrmentioning

confidence: 99%

Disruption of reelin signaling alters mammary gland morphogenesis

2011

Self Cite

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SUMMARYReelin signaling is required for appropriate cell migration and ductal patterning during mammary gland morphogenesis. Dab1, an intracellular adaptor protein activated in response to reelin signaling, is expressed in the developing mammary bud and in luminal epithelial cells in the adult gland. Reelin protein is expressed in a complementary pattern, first in the epithelium overlying the mammary bud during embryogenesis and then in the myoepithelium and periductal stroma in the adult. Deletion in mouse of either reelin or Dab1 induced alterations in the development of the ductal network, including significant retardation in ductal elongation, decreased terminal branching, and thickening and disorganization of the luminal wall. At later stages, some mutant glands overcame these early delays, but went on to exhibit enlarged and chaotic ductal morphologies and decreased terminal branching: these phenotypes are suggestive of a role for reelin in spatial patterning or structural organization of the mammary epithelium. Isolated mammary epithelial cells exhibited decreased migration in response to exogenous reelin in vitro, a response that required Dab1. These observations highlight a role for reelin signaling in the directed migration of mammary epithelial cells driving ductal elongation into the mammary fat pad and provide the first evidence that reelin signaling may be crucial for regulating the migration and organization of non-neural tissues.

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“…This raises the possibility that neurons are differentiating prematurely. To ensure that the cells in the PP and CP were not misplaced PCs, the expression of the VZ PC markers Nestin, Pax-6, Sall1, Sall3, and the SVZ marker SVET (subventricular tag) (Ott et al, 1996(Ott et al, , 2001Chapouton et al, 1999;Tarabykin et al, 2001;Anderson et al, 2002) was compared by in situ hybridization throughout the dorsal telencephalon from E10.0 until E16.5. No differences in the regional expression of the VZ or SVZ PC markers were observed between wild-type and mutant animals, indicating that the VZ and SVZ are molecularly distinct and confined to the ventricular surface (data not shown).…”

Section: Neurons Differentiate Prematurely In Tlxmentioning

confidence: 99%

TheTlxGene Regulates the Timing of Neurogenesis in the Cortex

Roy¹,

Kuznicki²,

Wu³

et al. 2004

J. Neurosci.

134

139

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The tailless (tlx) gene is a forebrain-restricted transcription factor. Tlx mutant animals exhibit a reduction in the size of the cerebral hemispheres and associated structures (Monaghan et al., 1997). Superficial cortical layers are specifically reduced, whereas deep layers are relatively unaltered (Land and Monaghan, 2003). To determine whether the adult laminar phenotype has a developmental etiology and whether it is associated with a change in proliferation/differentiation decisions, we examined the cell cycle and neurogenesis in the embryonic cortex. We found that there is a temporal and regional requirement for the Tlx protein in progenitor cells (PCs). Neurons prematurely differentiate at all rostrocaudal levels up to mid-neurogenesis in mutant animals. Heterozygote animals have an intermediate phenotype indicating there is a threshold requirement for Tlx in early cortical neurogenesis. Our studies indicate that PCs in the ventricular zone are sensitive to loss of Tlx in caudal regions only; however, PCs in the subventricular zone are altered at all rostrocaudal levels in tlx-deficient animals. Furthermore, we found that the cell cycle is shorter from embryonic day 9.5 in tlx Ϫ/Ϫ embryos. At mid-neurogenesis, the PC population becomes depleted, and late PCs have a longer cell cycle in tlx-deficient animals. Consequently, later generated structures, such as upper cortical layers, the dentate gyrus, and the olfactory bulbs, are severely reduced. These studies indicate that tlx is an essential intrinsic regulator in the decision to proliferate or differentiate in the developing forebrain.

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Differential Pax6 promoter activity and transcript expression during forebrain development

Cited by 29 publications

References 8 publications

Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms

Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms

Disruption of reelin signaling alters mammary gland morphogenesis

TheTlxGene Regulates the Timing of Neurogenesis in the Cortex

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