Hes1 Is Expressed in the Second Heart Field and Is Required for Outflow Tract Development

Background: Rapid growth of the embryonic heart occurs by addition of progenitor cells of the second heart field to the poles of the elongating heart tube. Failure or perturbation of this process leads to congenital heart defects. In order to provide further insight into second heart field development we characterized the insertion site of a transgene expressed in the second heart field and outflow tract as the result of an integration site position effect. Results: Here we show that the integration site of the A17-Myf5-nlacZ-T55 transgene lies upstream of Hes1, encoding a basic helix-loop-helix containing transcriptional repressor required for the maintenance of diverse progenitor cell populations during embryonic development. Transgene expression in a subset of Hes1 expression sites, including the CNS, pharyngeal epithelia, pericardium, limb bud and lung endoderm suggests that Hes1 is the endogenous target of regulatory elements trapped by the transgene. Hes1 is expressed in pharyngeal endoderm and mesoderm including the second heart field. Analysis of Hes1 mutant hearts at embryonic day 15.5 reveals outflow tract alignment defects including ventricular septal defects and overriding aorta. At earlier developmental stages, Hes1 mutant embryos display defects in second heart field proliferation, a reduction in cardiac neural crest cells and failure to completely extend the outflow tract. Conclusions: Hes1 is expressed in cardiac progenitor cells in the early embryo and is required for development of the arteria

A human RNA polymerase II subunit is encoded by a recently generated multigene family

BACKGROUND: The sequences encoding the yeast RNA polymerase II (RPB) subunits are single copy genes. RESULTS: While those characterized so far for the human (h) RPB are also unique, we show that hRPB subunit 11 (hRPB11) is encoded by a multigene family, mapping on chromosome 7 at loci p12, q11.23 and q22. We focused on two members of this family, hRPB11a and hRPB11b: the first encodes subunit hRPB11a, which represents the major RPB11 component of the mammalian RPB complex ; the second generates polypeptides hRPB11bα and hRPB11bβ through differential splicing of its transcript and shares homologies with components of the hPMS2L multigene family related to genes involved in mismatch-repair functions (MMR). Both hRPB11a and b genes are transcribed in all human tissues tested. Using an inter-species complementation assay, we show that only hRPB11bα is functional in yeast. In marked contrast, we found that the unique murine homolog of RPB11 gene maps on chromosome 5 (band G), and encodes a single polypeptide which is identical to subunit hRPB11a. CONCLUSIONS: The type hRPB11b gene appears to result from recent genomic recombination events in the evolution of primates, involving sequence elements related to the MMR apparatus

Kidd Blood Group and Urea Transport Function of Human Erythrocytes Are Carried by the Same Protein

International audienc

L'hétérochromatine et sa relation à la pathologie humaine

Le but de ce travail de thèse a été de mieux connaître l organisation, la composition et les fonctions de l hétérochromatine (HC) humaine. Cette partie du génome, caractérisée par son état très condensé et son inactivité transcriptionnelle, longtemps considérée comme inutile, demeure en effet mal connue. Ce travail a été essentiellement réalisé in situ, sur différents modèles d HC constitutive (télomères, régions centromériques) et facultative (vésicule sexuelle), dans des cellules normales et pathologiques. La première partie de ce travail, qui concerne l étude d une série de patients présentant une délétion de la région télomérique du chromosome 22, a conduit à la mise en évidence d un gène candidat potentiellement responsable du syndrome associé à cette délétion (syndrome 22q13). Il a aussi permis d émettre des hypothèses expliquant la tendance marquée des régions télomériques à la recombinaison et donc leur fréquente implication dans les réarrangements de ce type. La deuxième partie de ce travail a permis de démontrer que la protéine HP1, caractéristique de l HC constitutive, pouvait aussi être un constituant de l HC facultative de la vésicule sexuelle, permettant de penser que ces deux types d HC sont formés sur des bases communes. Enfin, la troisième partie, consacrée à l étude de la pathologique ICF (Immunodeficiency, Centromeric instability, Facial dysmorphy) a conduit à la mise en évidence d une certaine redondance entre les différents constituants de l HC. Cette étude a révélé la présence d une distribution altérée de la protéine HP1 à la phase G2 du cycle cellulaire, vraisemblablement liée au problème de condensation caractéristique du syndrome ICF. Enfin, cette étude a conduit à proposer l intervention des corps PML dans le processus de condensation de l HC qui précède la métaphase, fonction jusque là restée ignorée.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Etude structurale et fonctionnelle de la vésicule sexuelle au cours de la méiose masculine

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Mapping of the DOPA decarboxylase gene to the 11A band of the murine genome

International audienceA human DOPA decarboxylase (DDC) cDNA probe of 747 base pairs has been used to map the DDC gene by in situ hybridization on mouse metaphase chromosomes. This result indicates that the gene is located on band 11A, near the erythroblastosis oncogene B (erb b) locus. This provides evidence for a synteny group on mouse chromosome 11 and human chromosome 7

Cloning of Two Novel ABC Transporters Mapping on Human Chromosome 9

The family of ATP binding cassette (ABC) transporters or traffic ATPases is composed of several membrane-associated proteins that transport a great variety of solutes across cellular membranes. Two novel mammalian members of the family, ABC1 and ABC2, have been identified by a PCR-based approach. They belong to a group of traffic ATPases encoded as a single multifunctional protein, such as CFTR, STE 6, and P-glycoproteins. Their peculiar structural features and close relationship to ABC transporters involved in nodulation suggest that ABC1 and ABC2 define a novel subgroup of mammalian traffic ATPases

Assignment of the humanhap retinoic acid receptor RARβ gene to the p24 band of chromosome 3

International audienceThe human hap retinoic acid receptor RAR beta has been localized by in situ hybridization to the p24 band of chromosome 3

New gene in the homologous human 11q13-q14 and mouse 7F chromosomal regions

International audienceAlterations in the chromosomal region 11q13-11q14 are involved in several pathologies in which most of the key genes remain to be identified. In an effort to isolate as many candidates as possible, we are cloning genes from this region. We report here the mapping of a new sequence from 11q13.5-11q14. This sequence, designated D11S833E, putatively encodes a new gene, provisionally named GARP. We cloned its homologous sequence in the mouse and located it on Chromosome (Chr) 7, region F. The human and mouse genes belong to a conserved group of synteny. This, together with the similar conservation of the FGF and TYR genes, indicates that the human 11q13-q14 and mouse 7E-7F regions share homology