Abstract:
:Proximal-distal outgrowth of the vertebrate limb bud is regulated by the apical ectodermal ridge (AER), which forms at an invariant position along the dorsal-ventral (D/V) axis of the embryo. We have studied the genetic and cellular events that regulate AER formation in the mouse. In contrast to implications from previous studies in chick, we identified two distinct lineage boundaries in mouse ectoderm prior to limb bud outgrowth using a Cre/loxP-based fate-mapping approach and a novel retroviral cell-labeling technique. One border is transient and at the limit of expression of the ventral gene En1, which corresponds to the D/V midline of the AER, and the second border corresponds to the dorsal AER margin. Labeling of AER precursors using an inducible Cre showed that not all cells that initially express AER genes form the AER, indicating that signaling is required to maintain an AER phenotype. Misexpression of En1 at moderate levels specifically in the dorsal AER of transgenic mice was found to produce dorsally shifted AER fragments, whereas high levels of En1 abolished AER formation. In both cases, the dorsal gene Wnt7a was repressed in cells adjacent to the En1-expressing cells, demonstrating that signaling regulated by EN1 occurs across the D/V border. Finally, fate mapping of AER domains in these mutants showed that En1 plays a part in positioning and maintaining the two lineage borders.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Kimmel RA,Turnbull DH,Blanquet V,Wurst W,Loomis CA,Joyner ALsubject
Has Abstractpub_date
2000-06-01 00:00:00pages
1377-89issue
11eissn
0890-9369issn
1549-5477journal_volume
14pub_type
杂志文章abstract::A novel system to study early hematopoietic development is described. This report documents the in vitro capacity of murine embryonic stem (ES) cells to differentiate into hematopoietic precursors of most, if not all, of the colony-forming cells found in normal bone marrow. This system is used to correlate the genetic...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.5.728
更新日期:1991-05-01 00:00:00
abstract::Although the human U2 and U6 snRNA genes are transcribed by different RNA polymerases (i.e., RNA polymerases II and III, respectively), their promoters are very similar in structure. Both contain a proximal sequence element (PSE) and an octamer motif-containing enhancer, and these elements are interchangeable between ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.8.1477
更新日期:1991-08-01 00:00:00
abstract::The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1224204
更新日期:2004-10-01 00:00:00
abstract::In recent years several new mouse models for lung cancer have been described. These include models for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Tumorigenesis in these conditional mouse tumor models can be initiated in adult mice through Cre-recombinase-induced activation of oncogenic ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1284505
更新日期:2005-03-15 00:00:00
abstract::We report the discovery of mRNA 5'-leader trans-splicing (SL trans-splicing) in the chordates. In the ascidian protochordate Ciona intestinalis, the mRNAs of at least seven genes undergo trans-splicing of a 16-nucleotide 5'-leader apparently derived from a 46-nucleotide RNA that shares features with previously charact...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.865401
更新日期:2001-02-01 00:00:00
abstract::A cDNA library enriched for transcripts that accumulate from embryonic day 7 until day 1 posthatching was constructed from poly(A)+ RNA of chick optic lobe tissue. From this library, three recombinants were isolated that correspond to neural mRNAs appearing during the major period of synaptogenesis in the retinotectal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.699
更新日期:1987-09-01 00:00:00
abstract::The Ultrabithorax (Ubx) gene of Drosophila melanogaster encodes a family of UBX proteins that are thought to specify the developmental fates of segments in the posterior thorax and anterior abdomen by controlling the expression of a set of target genes. UBX proteins bind DNA in vitro, and they activate or repress diff...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.6.1044
更新日期:1990-06-01 00:00:00
abstract::The structurally related POU homeo domain proteins Pit-1 and Oct-2 activate pituitary- and lymphoid-specific transcription, respectively, by binding to similar AT-rich motifs in their target genes. In this study we identify bases critical for recognition and activation by Pit-1 and examine how small differences in Pit...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.1.43
更新日期:1990-01-01 00:00:00
abstract::The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the ex...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.294104
更新日期:2004-05-15 00:00:00
abstract::Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3442
更新日期:1998-11-01 00:00:00
abstract::The widespread class of RNA viruses that utilize internal ribosome entry sites (IRESs) for translation include poliovirus and Hepatitis C virus. To identify host factors required for IRES-dependent translation and viral replication, we performed a genome-wide RNAi screen in Drosophila cells infected with Drosophila C ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1267905
更新日期:2005-02-15 00:00:00
abstract::Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.2.111
更新日期:1987-04-01 00:00:00
abstract::Mammalian telomeres are coated by the sequence-specific, DNA-binding protein, TRF1, a negative regulator of telomere length. Previous results showed that ADP-ribosylation of TRF1 by tankyrase 1 released TRF1 from telomeres and promoted telomere elongation. We now show that loss of TRF1 from telomeres results in ubiqui...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1077103
更新日期:2003-06-01 00:00:00
abstract::The Bloom's syndrome gene (BLM) plays a pivotal role in the maintenance of genomic stability in somatic cells. It encodes a DNA helicase (BLM) of the RecQ family, but the exact function of BLM remains elusive. To study this question, we have cloned the BLM homolog of the frog Xenopus laevis (xBLM) and have raised anti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.822400
更新日期:2000-10-15 00:00:00
abstract::Dynamic assembly and disassembly of actin filaments is a major driving force for cell movements. Border cells in the Drosophila ovary provide a simple and genetically tractable model to study the mechanisms regulating cell migration. To identify new genes that regulate cell movement in vivo, we screened lethal mutatio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2028611
更新日期:2011-04-01 00:00:00
abstract::Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathway...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.16.2469
更新日期:1998-08-15 00:00:00
abstract::Early during Dictyostelium development a fundamental cell-fate decision establishes the anteroposterior (prestalk/prespore) axis. Signaling via the 7-transmembrane cAMP receptor CAR4 is essential for creating and maintaining a normal pattern; car4-null alleles have decreased levels of prestalk-specific mRNAs but enhan...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.16.2112
更新日期:1997-08-15 00:00:00
abstract::The ETS transcription factors perform distinct biological functions despite conserving a highly similar DNA-binding domain. One distinguishing property of a subset of ETS proteins is a conserved region of 80 amino acids termed the Pointed (PNT) domain. Using enzyme kinetics we determined that the Ets-1 PNT domain cont...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.950902
更新日期:2002-01-01 00:00:00
abstract::U4 and U6 small nuclear RNAs are associated by an extensive base-pairing interaction that must be disrupted and reformed with each round of splicing. U4 mutations within the U4/U6 interaction domain destabilize the complex in vitro and cause a cold-sensitive phenotype in vivo. Restabilization of the U4/U6 helix by dom...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.5.773
更新日期:1991-05-01 00:00:00
abstract::The transcription factor TFIIB plays a central role in preinitiation complex assembly, providing a bridge between promoter-bound TFIID and RNA Polymerase II. TFIIB possesses sequence-specific DNA-binding ability and interacts with the TFIIB-recognition element (BRE), present in many promoters. Here we show that the BR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.206901
更新日期:2001-11-15 00:00:00
abstract::Long understood as a bona fide tumor suppressor that safeguards the integrity of the genome via regulating numerous cellular outcomes, p53 may also exert its decisive and versatile functions by controlling DNA methylation. In this issue of Genes & Development, Tovy and colleagues (pp. 959-972) report that, in naïve mo...
journal_title:Genes & development
pub_type: 评论,杂志文章,评审
doi:10.1101/gad.302364.117
更新日期:2017-05-15 00:00:00
abstract::The sigma(28) protein is a member of the bacterial sigma(70)-family of transcription factors that directs RNA polymerase to flagellar late (class 3) promoters. The sigma(28) protein is regulated in response to flagellar assembly by the anti-sigma(28) factor FlgM. FlgM inhibits sigma(28)-dependent transcription of gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.380406
更新日期:2006-08-15 00:00:00
abstract::Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1267105
更新日期:2005-02-15 00:00:00
abstract::Estrogen receptor α (ER) is the major driver of ∼75% of breast cancers, and multiple ER targeting drugs are routinely used clinically to treat patients with ER+ breast cancer. However, many patients relapse on these targeted therapies and ultimately develop metastatic and incurable disease, and understanding the mecha...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.316646.118
更新日期:2018-09-01 00:00:00
abstract::The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.293704.116
更新日期:2017-01-15 00:00:00
abstract::We have purified and cloned a new splicing factor, KSRP. KSRP is a component of a multiprotein complex that binds specifically to an intronic splicing enhancer element downstream of the neuron-specific c-src N1 exon. This 75-kD protein induces the assembly of five other proteins, including the heterogeneous nuclear ri...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.8.1023
更新日期:1997-04-15 00:00:00
abstract::Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.862101
更新日期:2001-04-01 00:00:00
abstract::Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-04-15 00:00:00
abstract::Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1286005
更新日期:2005-04-01 00:00:00
abstract::The mammary tumor-associated proto-oncogene Wnt-1/int-1 encodes a secreted protein implicated in the regulation of neural development in vertebrates and segmental pattern in Drosophila. Using a PCR-based strategy, we isolated cDNAs encoding six novel, related proteins that are expressed in fetal mice. Predicted protei...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.12b.2319
更新日期:1990-12-01 00:00:00