Abstract:
:Keratinocyte growth factor (KGF), also known as fibroblast growth factor 7 (FGF7), is synthesized by skin fibroblasts. However, its mitogenic activity is on skin keratinocytes, where it is the most potent growth factor identified thus far. To explore KGF's function in vivo, we used embryonic stem cell technology to generate mice lacking KGF. Over time, their fur developed a matted appearance, very similar to that of the rough mouse, whose recessive mutation maps at or near the KGF locus on mouse chromosome 2. In contrast to the recently reported transforming growth factor-alpha (TGF-alpha) and FGF5 knockouts, which showed defects in the follicle outer-root sheath and the hair growth cycle, respectively, the hair defect in the KGF knockout seemed to be restricted to the cells giving rise to the hair shaft. Thus, we have uncovered a third, and at least partially nonoverlapping, growth factor pathway involved in orchestrating hair follicle growth and/or differentiation. Surprisingly, the absence of KGF resulted in no abnormalities in epidermal growth or wound healing. This was true even when we engineered double knockout mice, null for both KGF and TGF-alpha, two factors that are increased dramatically in the normal wound-healing process. Whereas we found no evidence of compensatory changes at the mRNA level of wounded knockout mice, these data imply that the regulation of epidermal growth is complex and involves a number of growth stimulatory factors that go beyond what are thought to be the major paracrine and autocrine growth factors. We suggest that the redundancy in epidermal growth and wound healing is likely to stem from the vitality of these functions to the organism, a feature that is not a consideration for the hair follicle.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Guo L,Degenstein L,Fuchs Edoi
10.1101/gad.10.2.165subject
Has Abstractpub_date
1996-01-15 00:00:00pages
165-75issue
2eissn
0890-9369issn
1549-5477journal_volume
10pub_type
杂志文章abstract::De novo chromatin assembly into regularly spaced nucleosomal arrays is essential for eukaryotic genome maintenance and inheritance. The Anti-Silencing Function 1 protein (ASF1) has been shown to be a histone chaperone, participating in DNA-replication-coupled nucleosome assembly. We show that mutations in the Drosophi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.231202
更新日期:2002-10-15 00:00:00
abstract::DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.301404
更新日期:2004-06-15 00:00:00
abstract::Mesoderm induction assays in Xenopus have implicated growth factors such as activin, Vg1, Xwnt-8, and noggin as important in directing the formation of dorsal mesoderm (Spemann's organizer). Because these growth factors are structurally very different, they presumably act through distinct cell surface receptors that i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3038
更新日期:1995-12-15 00:00:00
abstract::The X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals. Over recent years an important goal has been to understand how Xist is regulated at the initiation of X inactivation. Here we report the analysis of a series of targeted mutations at the 5' end o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271203
更新日期:2003-09-01 00:00:00
abstract::In vivo experiments have demonstrated that the ribosomal protein L32 of Saccharomyces cerevisiae brings about the inhibition of splicing of the transcript of its own gene through an RNA structure comprised largely of the first exon. We now show that L32, itself, binds specifically to this RNA. Splicing of the RPL32 tr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.2.211
更新日期:1994-01-01 00:00:00
abstract::The mammalian high mobility group proteins HMG1 and HMG2 are abundant, chromatin-associated proteins whose cellular function is not known. In this study we show that these proteins can substitute for the prokaryotic DNA-bending protein HU in promoting the assembly of the Hin invertasome, an intermediate structure in H...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.8.1521
更新日期:1993-08-01 00:00:00
abstract::The rpoH gene of Escherichia coli encodes sigma 32, the 32-kD sigma-factor responsible for the heat-inducible transcription of the heat shock genes. rpoH is transcribed from at least three promoters. Two of these promoters are recognized by RNA polymerase containing sigma 70, the predominant sigma-factor. We purified ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1462
更新日期:1989-09-01 00:00:00
abstract::By studying neuroectoderm formation in the absence of mesoderm and mesectoderm in mutants of the zygotic genes snail and twist, we have found that the number of neuroblasts is not reduced in these mutants, suggesting that mesoderm and mesectoderm are not essential for the initiation of neural development. The position...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.9.1577
更新日期:1991-09-01 00:00:00
abstract::Protein kinases are key regulators of cellular processes. In spite of considerable effort, a full understanding of the pathways they participate in remains elusive. We globally investigated the proteins that interact with the majority of yeast protein kinases using protein microarrays. Eighty-five kinases were purifie...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1998811
更新日期:2011-04-01 00:00:00
abstract::Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.6.1072
更新日期:1993-06-01 00:00:00
abstract::AU-rich elements (AREs, usually containing repeated copies of AUUUA), when present in the 3'-untranslated regions (UTRs) of many mammalian mRNAs, confer instability on their host RNA molecules. The viral small nuclear RNA (snRNA) Herpesvirus saimiri U RNA 1 (HSUR 1) also contains an AUUUA-rich sequence. Here, we repor...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.19.2557
更新日期:1997-10-01 00:00:00
abstract::In Drosophila germ cells, PIWI-interacting RNAs (piRNAs) are amplified through a PIWI slicer-dependent feed-forward loop termed the ping-pong cycle, yielding secondary piRNAs. However, the detailed mechanism remains poorly understood, largely because an ex vivo model system amenable to biochemical analyses has not bee...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.283929.116
更新日期:2016-07-15 00:00:00
abstract::TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in exci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.194829.112
更新日期:2012-08-01 00:00:00
abstract::Unusually for a eukaryote, genes transcribed by RNA polymerase II (pol II) in Trypanosoma brucei are arranged in polycistronic transcription units. With one exception, no pol II promoter motifs have been identified, and how transcription is initiated remains an enigma. T. brucei has four histone variants: H2AZ, H2BV, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1790409
更新日期:2009-05-01 00:00:00
abstract::The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that are bound and activated by oxysterols. These receptors serve as sterol sensors to regulate the transcription of gene products that control intracellular cholesterol homeostasis through catabolism and transport. In this report, we...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.844900
更新日期:2000-11-15 00:00:00
abstract::The subdivision of the lateral mesoderm into a visceral (splanchnic) and a somatic layer is a crucial event during early mesoderm development in both arthropod and vertebrate embryos. In Drosophila, this subdivision leads to the differential development of gut musculature versus body wall musculature. Here we report t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.917101
更新日期:2001-11-01 00:00:00
abstract::The secreted Drosophila Hedgehog (Hh) protein induces transcription of specific genes by an unknown mechanism that requires the serpentine transmembrane protein Smoothened (Smo) and the transcription factor Cubitus interruptus (Ci). Protein kinase A (PKA) has been implicated in the mechanism of Hh signal transduction ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.17.2250
更新日期:1997-09-01 00:00:00
abstract::RNA polymerase II nascent transcripts are capped during pausing before elongation. Here we report that hSPT5, the human homolog of yeast elongation factor SPT5, interacts directly with the capping enzyme. hSPT5 stimulated capping enzyme guanylylation and mRNA capping by severalfold. Although RNA 5'-triphosphatase acti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.14.1774
更新日期:1999-07-15 00:00:00
abstract::Hundreds of microRNAs (miRNAs) have been discovered in metazoans and plants, and understanding of their biogenesis has advanced dramatically; however, relatively little is known about the cofactors necessary for miRNA regulation of target gene expression. In Caenorhabditis elegans, the conserved miRNA let-7 and its pa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.17153811
更新日期:2011-10-01 00:00:00
abstract::Riboswitches are RNA elements that undergo a shift in structure in response to binding of a regulatory molecule. These elements are encoded within the transcript they regulate, and act in cis to control expression of the coding sequence(s) within that transcript; their function is therefore distinct from that of small...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1747308
更新日期:2008-12-15 00:00:00
abstract::The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TL...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.254904.114
更新日期:2015-02-15 00:00:00
abstract::We have studied the sequence requirements for 3'-end formation of rDNA transcripts in a cell-free system and show that the generation of correct ends of mouse pre-rRNA is brought about by a two-step process that involves a bona fide termination reaction, followed by a specific trimming of the primary transcript by 10 ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.2.224
更新日期:1989-02-01 00:00:00
abstract::Overexpression of the type II transmembrane serine protease matriptase is a highly consistent feature of human epithelial tumors. Here we show that matriptase possesses a strong oncogenic potential when unopposed by its endogenous inhibitor, HAI-1. Modest orthotopic overexpression of matriptase in the skin of transgen...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1300705
更新日期:2005-08-15 00:00:00
abstract::Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.6.770
更新日期:1989-06-01 00:00:00
abstract::GRF2, an abundant yeast protein of Mr approximately 127,000, binds to the GAL upstream activating sequence (UASG) and creates a nucleosome-free region of approximately 230 bp. Purified GRF2 binds to sequences found in many other UASs, in the 35S rRNA enhancer, at centromeres, and at telomeres. Although GRF2 stimulates...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.503
更新日期:1990-04-01 00:00:00
abstract::Actin is associated with all three nuclear RNA polymerases and acts in concert with nuclear myosin I (NM1) to drive transcription. Practically nothing is known regarding the state of actin and the functional interplay of actin and NM1 in transcription. Here we show that actin and NM1 act in concert to promote RNA poly...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.455908
更新日期:2008-02-01 00:00:00
abstract::The heterochromatin-like structure formed by the yeast silent information regulator complex (SIR) represses transcription at the silent mating type loci and telomeres. Here, we report that tight protein-DNA complexes induce ectopic recruitment of the SIR complex, promoting gene silencing and changes in subnuclear loca...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.611011
更新日期:2011-07-01 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::To understand how chromosome shapes are determined by actions of condensins and cohesin, we devised a series of protocols in which their levels are precisely changed in Xenopus egg extracts. When the relative ratio of condensin I to II is forced to be smaller, embryonic chromosomes become shorter and thicker, being re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2060311
更新日期:2011-07-15 00:00:00
abstract::We report a new role for Wnt signaling in the vertebrate embryo: the induction of neural tissue from ectoderm. Early expression of mouse wnt8, Xwnt8, beta-catenin, or dominant-negative GSK3 induces the expression of neural-specific markers and inhibits the expression of Bmp4 in Xenopus ectoderm. We show that Wnt8, but...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.23.3149
更新日期:1999-12-01 00:00:00