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S Tomarev

Publications and source records attributed to S Tomarev.

5 recordsLinked to original sources
PubMed1999

Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation.

We have identified a novel vertebrate homolog of the Drosophila gene dachshund, Dachshund2 (Dach2). Dach2 is expressed in the developing somite prior to any myogenic genes with an expression profile similar to Pax3, a gene previously shown to induce muscle differentiation. Pax3 and Dach2 participate in a positive regulatory feedback loop, analogous to a feedback loop that exists in Drosophila between the Pax gene eyeless (a Pax6 homolog) and the Drosophila dachshund gene. Although Dach2 alone is unable to induce myogenesis, Dach2 can synergize with Eya2 (a vertebrate homolog of the Drosophila gene eyes absent) to regulate myogenic differentiation. Moreover, Eya2 can also synergize with Six1 (a vertebrate homolog of the Drosophila gene sine oculis) to regulate myogenesis. This synergistic regulation of muscle development by Dach2 with Eya2 and Eya2 with Six1 parallels the synergistic regulation of Drosophila eye formation by dachshund with eyes absent and eyes absent with sine oculis. This synergistic regulation is explained by direct physical interactions between Dach2 and Eya2, and Eya2 and Six1 proteins, analogous to interactions observed between the Drosophila proteins. This study reveals a new layer of regulation in the process of myogenic specification in the somites. Moreover, we show that the Pax, Dach, Eya, and Six genetic network has been conserved across species. However, this genetic network has been used in a novel developmental context, myogenesis rather than eye development, and has been expanded to include gene family members that are not directly homologous, for example Pax3 instead of Pax6.

Amino Acid Sequence↗
PubMed1998

Chicken Eyes absent 2 gene: isolation and expression pattern during development.

In all vertebrates studied (human, mouse, chicken), there are at least three genes related to Drosophila eyes absent (eya) gene. The chicken Eyes absent 2 (Eya2) cDNA was isolated from 14 day embryonic chicken lenses, and a complete open reading frame encoding a 59 kDa protein was elucidated. The chicken Eya2 protein is moderately conserved and 78-82% identical to the mouse and human Eya2. The Eya2 gene demonstrated a dynamic expression pattern in different tissues of diverse embryological origin. Expression of Eya2 was first detected at Hamburger and Hamilton stage 9 in the foregut. At later stages of development, Eya2 mRNA was detected in neural crest derivatives (dorsal root ganglia, branchial arches and cranial nerve ganglia). In the cranial placodes, expression of Eya2 was first detected in the nasal pit at stage 13. In the eye, expression of Eya2 was first convincingly detected in neural retina at stage 24 (day 4). The highest level of Eya2 mRNA in the lens was detected around day 9. Eya2 is also expressed in the cornea and iris. Therefore, chicken Eya2, as well as mouse Eya2, is expressed relatively early in the nasal (but not in the lens) placode and may mediate induction of the nasal placode. Expression of Eya2 in the wing and limb buds is consistent with its proposed role in the patterning of limb connective tissues.

Amino Acid Sequence↗
PubMed1997

Pax-6, Prox 1, and Chx10 homeobox gene expression correlates with phenotypic fate of retinal precursor cells.

PURPOSE: To study the expression patterns of the homeobox genes Pax-6, Prox 1, and Chx10 during chick retinal development in vivo and in vitro. METHODS: Sections of paraformaldehyde-fixed, paraffin-embedded eyes were obtained at a range of developmental stages. In situ hybridization was carried out on tissue sections using digoxigenin-labeled sense and antisense RNA probes that recognize chicken Pax-6 and Prox 1 (whose sequences were already available), and chicken Chx10 (which was cloned and sequenced as part of this study). Selected developmental stages were also studied by immunocytochemistry with antibodies against Pax-6 and Prox 1, and by Northern blot analysis using 32P-labeled probes. RESULTS: Until embryonic day (ED) 5, in situ hybridization shows widespread, diffuse distribution of all three genes. Between ED 6 and ED 8, however, they acquire distinct, topographically specific patterns of expression. The Prox 1 signal is predominantly expressed in the prospective horizontal cell layer of the neuroepithelium, decreases vitreally, and is absent from ganglion cells and the prospective photoreceptor layer. Pax-6 is strongly expressed only in the prospective ganglion-cell and amacrine-cell regions at the same stages, and is not detected in prospective photoreceptors. Chx10 expression becomes concentrated in the future bipolar-cell region of the inner nuclear layer. Similar patterns are maintained by ED 15 through ED 18, after cell differentiation has taken place. Pax-6 and Prox 1 immunoreactive materials showed nuclear localization and a pattern of laminar distribution equivalent to that seen by in situ hybridization. CONCLUSIONS: These results suggest that the differentiated fate of retinal precursor cells may be influenced by Pax-6, Prox 1, or Chx10, this hypothesis is now being tested using dissociated chick embryo retinal cell cultures.

Amino Acid Sequence↗
PubMed1996

Glutathione S-transferase M1 genotype and age-related cataracts. Lack of association in an Italian population.

PURPOSE: To investigate possible associations between the gene number and allelic forms of glutathione S-transferase M1 (GSTM1) and the occurrence of nucleic and cortical age-related cataracts. METHODS: Patients with cortical cataract, nuclear cataract, mixed and cortical cataract, and no cataract were sytematically selected from subjects evaluated in the Italian-American Study of the Natural History of Age-Related Cataract. The patients were typed for the A, B, and null alleles of GSTM1 using a variation of the amplification refractory mutation system. RESULTS: Forty-nine percent of patients (50/102) with cortical cataracts, 45% (13/29) with nuclear cataracts, 51% (36/71) with mixed nuclear and cortical cataracts, and 50% of controls (49/98) were homozygous for the null GSTM1 allele. Twenty-five percent of patients (26/102) with cortical cataracts, 24% (7/29) with nuclear cataracts, 31% with mixed nuclear and cortical cataracts, and 27% of controls (26/98) displayed only the A allele for GSTM1. Twenty-four percent of patients (24/102) with cortical cataract, 24% (7/29) with nuclear cataracts, 14% (10/71) with mixed nuclear and cortical cataract, and 18% of controls showed only the B allele for GSTM1. Two percent of patients (2/102) with cortical cataracts, 7% (2/29) with nuclear cataracts, 4% (3/71) with mixed nuclear and cortical cataracts, and 5% of controls (5/98) showed both A and B alleles for GSTM1. CONCLUSIONS: No associations between the GSTM1 alleles, including the null allele, and cataracts were detected in this study.

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