, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 54

Publication Record

Connections

Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina.
Clark AM, Yun S, Veien ES, Wu YY, Chow RL, Dorsky RI, Levine EM
(2008) Brain Res 1192: 99-113
MeSH Terms: Animals, Cell Differentiation, Cell Line, Conserved Sequence, Down-Regulation, Evolution, Molecular, Eye Proteins, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins, Humans, Mice, Mice, Knockout, Promoter Regions, Genetic, RNA, Messenger, Regulatory Elements, Transcriptional, Repressor Proteins, Retina, Stem Cells, Transcription Factors, Up-Regulation, Vertebrates, Zebrafish
Show Abstract · Added November 2, 2015
Chx10/Vsx2 and Vsx1 are the only Paired-like CVC (Prd-L:CVC) homeobox genes in the mouse genome. Both are expressed in the retina and have important but distinct roles in retinal development. Mutations in Chx10/Vsx2 cause reduced retinal progenitor cell (RPC) proliferation and an absence of bipolar cells, while mutations in Vsx1 impair differentiation of cone bipolar cells. Given their structural similarities and importance in retinal development, we sought to determine if a regulatory interaction exists between these genes and whether inactivation of both genes blocks initiation of retinal development. We found that Chx10/Vsx2 binds to a specific sequence in the Vsx1 5'-intergenic region and represses the activity of a luciferase reporter under the control of the Vsx1 promoter. This is consistent with our observation that there is an inverse relationship between the levels of Chx10/Vsx2 and Vsx1 immunostaining within the bipolar cell class. Furthermore, Vsx1 mRNA is upregulated in the RPCs of Chx10/Vsx2 deficient mice and zebrafish embryos injected with a chx10/vsx2 morpholino. In mice deficient for both Chx10/Vsx2 and Vsx1 and zebrafish embryos co-injected with chx10/Vsx2 and vsx1 morpholinos, the changes in embryonic retinal development and marker expression are similar in magnitude to embryos with Chx10/Vsx2 loss of function only. From these studies, we propose that Vsx1 is a direct target of Chx10/Vsx2-mediated transcriptional repression. Although Vsx1 mRNA is upregulated in Chx10/Vsx2 deficient RPCs, Vsx1 does not genetically compensate for loss of Chx10/Vsx2, demonstrating that Prd-L:CVC genes, although important, are not absolutely required to initiate retinal development.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Cell-intrinsic regulators of proliferation in vertebrate retinal progenitors.
Levine EM, Green ES
(2004) Semin Cell Dev Biol 15: 63-74
MeSH Terms: Animals, Cell Cycle, Cell Cycle Proteins, Cell Differentiation, Cell Division, G1 Phase, Gene Expression Regulation, Developmental, Genes, Homeobox, Humans, Models, Biological, Retina, Stem Cells, Vertebrates
Show Abstract · Added November 2, 2015
The proliferative expansion of retinal progenitor cells (RPCs) is a fundamental mechanism of growth during vertebrate retinal development. Over the past couple of years, significant progress has been made in identifying genes expressed in RPCs that are essential for their proliferation, and the molecular mechanisms are beginning to be resolved. In this review, we highlight recent studies that have identified regulatory components of the RPC cell cycle machinery and implicate a set of homeobox genes as key regulators of proliferative expansion in the retina.
0 Communities
1 Members
0 Resources
13 MeSH Terms
The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites.
Mankoo BS, Skuntz S, Harrigan I, Grigorieva E, Candia A, Wright CV, Arnheiter H, Pachnis V
(2003) Development 130: 4655-64
MeSH Terms: Animals, Body Patterning, Bone Development, Bone and Bones, Embryo, Mammalian, Epithelium, Gene Expression Regulation, Developmental, Genes, Homeobox, In Situ Hybridization, Mice, Mice, Transgenic, Morphogenesis, Muscle, Skeletal, Phenotype, Somites
Show Abstract · Added June 11, 2010
The paraxial mesoderm of the somites of the vertebrate embryo contains the precursors of the axial skeleton, skeletal muscles and dermis. The Meox1 and Meox2 homeobox genes are expressed in the somites and their derivatives during embryogenesis. Mice homozygous for a null mutation in Meox1 display relatively mild defects in sclerotome derived vertebral and rib bones, whereas absence of Meox2 function leads to defective differentiation and morphogenesis of the limb muscles. By contrast, mice carrying null mutations for both Meox genes display a dramatic and wide-ranging synthetic phenotype associated with extremely disrupted somite morphogenesis, patterning and differentiation. Mutant animals lack an axial skeleton and skeletal muscles are severely deficient. Our results demonstrate that Meox1 and Meox2 genes function together and upstream of several genetic hierarchies that are required for the development of somites. In particular, our studies place Meox gene function upstream of Pax genes in the regulation of chondrogenic and myogenic differentiation of paraxial mesoderm.
1 Communities
1 Members
0 Resources
15 MeSH Terms
Experimental control of pancreatic development and maintenance.
Holland AM, Hale MA, Kagami H, Hammer RE, MacDonald RJ
(2002) Proc Natl Acad Sci U S A 99: 12236-41
MeSH Terms: Animals, Bacterial Proteins, Carrier Proteins, Doxycycline, Female, Gene Expression, Genes, Homeobox, Genes, Reporter, Glucose, Green Fluorescent Proteins, Homeodomain Proteins, Insulin, Luminescent Proteins, Mice, Mice, Knockout, Mice, Transgenic, Pancreas, Phenotype, Pregnancy, Tetracycline, Trans-Activators
Show Abstract · Added November 6, 2013
To investigate the role of the HOX-like homeoprotein PDX1 in the formation and maintenance of the pancreas, we have genetically engineered mice so that the only source of PDX1 is a transgene that can be controlled by the application of tetracycline or its analogue doxycycline. In these mice the coding region for the tetracycline-regulated transactivator (tTA(off)) has replaced the coding region of the endogenous Pdx1 gene to ensure correct temporal and spatial expression of the regulatable transactivator. In the absence of doxycycline, tTA(off) activates the transcription of a bicistronic transgene encoding PDX1 and an enhanced green fluorescent protein reporter, which acts as a visual marker of transgene expression in living cells. Expression of the transgene-encoded PDX1 rescues the Pdx1-null phenotype; the pancreata of these mice develop and function normally. The rescue is conditional; doxycycline-mediated repression of the transgenic Pdx1 throughout gestation recapitulates the Pdx1 null phenotype. Moreover, application of doxycycline at mid-pancreogenesis blocks further development. Adult animals of the rescue genotype that were treated with doxycycline for 3 weeks shut off Pdx1 expression, decreased insulin production, and lost the ability to maintain glucose homeostasis. These results demonstrate the feasibility of controlling the formation of an organ during embryogenesis in utero and the maintenance of the mature organ through the experimental manipulation of a key developmental regulator.
0 Communities
1 Members
0 Resources
21 MeSH Terms
A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide deletion in the promoter underlies Guttmacher syndrome.
Innis JW, Goodman FR, Bacchelli C, Williams TM, Mortlock DP, Sateesh P, Scambler PJ, McKinnon W, Guttmacher AE
(2002) Hum Mutat 19: 573-4
MeSH Terms: Abnormalities, Multiple, Alleles, Base Sequence, Female, Foot Deformities, Congenital, Genes, Homeobox, Genitalia, Hand Deformities, Congenital, Homeodomain Proteins, Humans, Male, Mutation, Missense, Pedigree, Promoter Regions, Genetic, Sequence Deletion, Syndrome
Show Abstract · Added June 9, 2010
Guttmacher syndrome, a dominantly inherited combination of distal limb and genital tract abnormalities, has several features in common with hand-foot-genital syndrome (HFGS), including hypoplastic first digits and hypospadias. The presence of features not seen in HFGS, however, including postaxial polydactyly of the hands and uniphalangeal 2(nd) toes with absent nails, suggests that it represents a distinct entity. HFGS is caused by mutations in the HOXA13 gene. We have therefore re-investigated the original Guttmacher syndrome family, and have found that affected individuals are heterozygous for a novel missense mutation in the HOXA13 homeobox (c.1112A>T; homeodomain residue Q50L), which arose on an allele already carrying a novel 2-bp deletion (-78-79delGC) in the gene's highly conserved promoter region. This deletion produces no detectable abnormalities on its own, but may contribute to the phenotype in the affected individuals. The missense mutation, which alters a key residue in the recognition helix of the homeodomain, is likely to perturb HOXA13's DNA-binding properties, resulting in both a loss and a specific gain of function.
Copyright 2002 Wiley-Liss, Inc.
1 Communities
1 Members
0 Resources
16 MeSH Terms
Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.
Goodman FR, Bacchelli C, Brady AF, Brueton LA, Fryns JP, Mortlock DP, Innis JW, Holmes LB, Donnenfeld AE, Feingold M, Beemer FA, Hennekam RC, Scambler PJ
(2000) Am J Hum Genet 67: 197-202
MeSH Terms: Abnormalities, Multiple, Child, Codon, Nonsense, DNA Mutational Analysis, Female, Foot Deformities, Congenital, Genes, Homeobox, Hand Deformities, Congenital, Homeodomain Proteins, Humans, Infant, Male, Molecular Sequence Data, Mutation, Mutation, Missense, Pedigree, Phenotype, Radiography, Sequence Deletion, Syndrome, Urogenital Abnormalities
Show Abstract · Added June 9, 2010
Hand-foot-genital syndrome (HFGS) is a rare, dominantly inherited condition affecting the distal limbs and genitourinary tract. A nonsense mutation in the homeobox of HOXA13 has been identified in one affected family, making HFGS the second human syndrome shown to be caused by a HOX gene mutation. We have therefore examined HOXA13 in two new and four previously reported families with features of HFGS. In families 1, 2, and 3, nonsense mutations truncating the encoded protein N-terminal to or within the homeodomain produce typical limb and genitourinary abnormalities; in family 4, an expansion of an N-terminal polyalanine tract produces a similar phenotype; in family 5, a missense mutation, which alters an invariant domain, produces an exceptionally severe limb phenotype; and in family 6, in which limb abnormalities were atypical, no HOXA13 mutation could be detected. Mutations in HOXA13 can therefore cause more-severe limb abnormalities than previously suspected and may act by more than one mechanism.
1 Communities
1 Members
0 Resources
21 MeSH Terms
Mox2 is a component of the genetic hierarchy controlling limb muscle development.
Mankoo BS, Collins NS, Ashby P, Grigorieva E, Pevny LH, Candia A, Wright CV, Rigby PW, Pachnis V
(1999) Nature 400: 69-73
MeSH Terms: Animals, Antigens, CD, Antigens, Surface, Embryonic and Fetal Development, Extremities, Gene Expression, Gene Targeting, Genes, Homeobox, Genes, Reporter, Male, Mesoderm, Mice, Mice, Inbred C57BL, Morphogenesis, Muscle, Skeletal, Mutation, Myogenin
Show Abstract · Added June 11, 2010
The skeletal muscles of the limbs develop from myogenic progenitors that originate in the paraxial mesoderm and migrate into the limb-bud mesenchyme. Among the genes known to be important for muscle development in mammalian embryos are those encoding the basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs; MyoD, Myf5, myogenin and MRF4) and Pax3, a paired-type homeobox gene that is critical for the development of limb musculature. Mox1 and Mox2 are closely related homeobox genes that are expressed in overlapping patterns in the paraxial mesoderm and its derivatives. Here we show that mice homozygous for a null mutation of Mox2 have a developmental defect of the limb musculature, characterized by an overall reduction in muscle mass and elimination of specific muscles. Mox2 is not needed for the migration of myogenic precursors into the limb bud, but it is essential for normal appendicular muscle formation and for the normal regulation of myogenic genes, as demonstrated by the downregulation of Pax3 and Myf5 but not MyoD in Mox2-deficient limb buds. Our findings show that the MOX2 homeoprotein is an important regulator of vertebrate limb myogenesis.
1 Communities
1 Members
0 Resources
17 MeSH Terms
Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells.
Sussel L, Kalamaras J, Hartigan-O'Connor DJ, Meneses JJ, Pedersen RA, Rubenstein JL, German MS
(1998) Development 125: 2213-21
MeSH Terms: Animals, Blood Glucose, Cell Differentiation, Cell Lineage, DNA-Binding Proteins, Diabetes Mellitus, Eye Proteins, Gene Targeting, Genes, Homeobox, Glucagon, Homeodomain Proteins, Immunohistochemistry, Insulin, Islets of Langerhans, Mice, Mutation, PAX6 Transcription Factor, Paired Box Transcription Factors, Pancreatic Polypeptide, Repressor Proteins, Somatostatin, Transcription Factors, Zebrafish Proteins
Show Abstract · Added July 7, 2015
The endocrine pancreas is organized into clusters of cells called islets of Langerhans comprising four well-defined cell types: alpha beta, delta and PP cells. While recent genetic studies indicate that islet development depends on the function of an integrated network of transcription factors, the specific roles of these factors in early cell-type specification and differentiation remain elusive. Nkx2.2 is a member of the mammalian NK2 homeobox transcription factor family that is expressed in the ventral CNS and the pancreas. Within the pancreas, we demonstrate that Nkx2.2 is expressed in alpha, beta and PP cells, but not in delta cells. In addition, we show that mice homozygous for a null mutation of Nkx2.2 develop severe hyperglycemia and die shortly after birth. Immunohistochemical analysis reveals that the mutant embryos lack insulin-producing beta cells and have fewer glucagon-producing alpha cells and PP cells. Remarkably, in the mutants there remains a large population of islet cells that do not produce any of the four endocrine hormones. These cells express some beta cell markers, such as islet amyloid polypeptide and Pdx1, but lack other definitive beta cell markers including glucose transporter 2 and Nkx6.1. We propose that Nkx2.2 is required for the final differentiation of pancreatic beta cells, and in its absence, beta cells are trapped in an incompletely differentiated state.
0 Communities
0 Members
0 Resources
23 MeSH Terms
Vsx-1 and Vsx-2: differential expression of two paired-like homeobox genes during zebrafish and goldfish retinogenesis.
Passini MA, Levine EM, Canger AK, Raymond PA, Schechter N
(1997) J Comp Neurol 388: 495-505
MeSH Terms: Amino Acid Sequence, Animals, Eye, Eye Proteins, Fish Proteins, Gene Expression Regulation, Developmental, Genes, Homeobox, Goldfish, Homeodomain Proteins, Molecular Sequence Data, Retina, Sequence Homology, Amino Acid, Zebrafish, Zebrafish Proteins
Show Abstract · Added November 2, 2015
Vsx-1 and Vsx-2 are two homeobox genes that were cloned originally from an adult goldfish retinal library. They are members of the paired-like:CVC gene family, which is characterized by the presence of a paired homeodomain and an additional conserved region, termed the CVC domain. To analyze the possible roles for Vsx-1 and Vsx-2 in eye development, we used in situ hybridization to examine their expression patterns in zebrafish and goldfish embryos. Vsx-2 is initially expressed by proliferating neuroepithelial cells of the presumptive neural retina, then it is down-regulated as differentiation begins, and it is finally reexpressed at later stages of differentiation in a subset of cells, presumed to be bipolar cells, in the inner nuclear layer. In contrast, Vsx-1 is expressed only weakly in undifferentiated, presumptive neural retina and is then up-regulated selectively in presumptive bipolar cells at early stages of differentiation (when Vsx-2 is turned off), before decreasing to an intermediate level, which is maintained in the differentiated (adult) retina. The restricted expression patterns of Vsx-2 correspond to the observed phenotypes in mice with the ocular retardation mutation (orJ), further supporting the notion that Vsx-2 and Chx10 are homologues. The sequential complimentary and then corresponding expression patterns of Vsx-1 and Vsx-2 suggest that these similar transcription factors may be recruited for partially overlapping, but distinct, functions during the development of the retina.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Vsx-1 and Vsx-2: two Chx10-like homeobox genes expressed in overlapping domains in the adult goldfish retina.
Levine EM, Passini M, Hitchcock PF, Glasgow E, Schechter N
(1997) J Comp Neurol 387: 439-48
MeSH Terms: Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, Eye Proteins, Fish Proteins, Genes, Homeobox, Goldfish, Homeodomain Proteins, Molecular Sequence Data, RNA, Messenger, Recombinant Proteins, Retina, Sequence Alignment, Sequence Homology, Amino Acid, Transcription Factors, Transcription, Genetic
Show Abstract · Added November 2, 2015
The genetic linkages of the murine ocular retardation mutation with the Chx10 gene and the murine small eye mutation with the Pax-6 gene has demonstrated the importance of Paired class homeobox genes in the development of the mammalian retina. Previously, we identified a Paired-class homeobox gene, Vsx-1, whose expression in the adult goldfish retina is restricted to the inner nuclear layer (INL) and to postmitotic, differentiating progenitor cells in the growth zone at the retinal peripheral margin, where neurogenesis continues throughout life. Here, we report the molecular cloning and expression pattern of a new Paired class homeobox gene, Vsx-2, in the adult goldfish retina. Like Vsx-1, Vsx-2 expression is highly restricted to the retina in the adult goldfish and overlaps with Vsx-1 expression in the mature INL. At the peripheral margin, Vsx-2 is expressed in mitotically active neuronal progenitors and is downregulated as these cells become postmitotic and begin to differentiate. Comparison of the amino acid sequences of Vsx-2, Vsx-1, Chx10, and C. elegans ceh-10 reveal a conserved homeodomain and a unique domain termed the CVC domain. The similarities of the Vsx-2, Vsx-1, and Chx10 expression patterns suggest that genes containing the CVC domain have conserved functions during retinal development in vertebrates.
0 Communities
1 Members
0 Resources
17 MeSH Terms