Biomedical subjects

B I Meyer

Publications and source records attributed to B I Meyer.

4 recordsLinked to original sources

PubMed1998

Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development.

The cytosolic protein APAF1, human homolog of C. elegans CED-4, participates in the CASPASE 9 (CASP9)-dependent activation of CASP3 in the general apoptotic pathway. We have generated by gene trap a null allele of the murine Apaf1. Homozygous mutants die at embryonic day 16.5. Their phenotype includes severe craniofacial malformations, brain overgrowth, persistence of the interdigital webs, and dramatic alterations of the lens and retina. Homozygous embryonic fibroblasts exhibit reduced response to various apoptotic stimuli. In situ immunodetection shows that the absence of Apaf1 protein prevents the activation of Casp3 in vivo. In agreement with the reported function of CED-4 in C. elegans, this phenotype can be correlated with a defect of apoptosis. Our findings suggest that Apaf1 is essential for Casp3 activation in embryonic brain and is a key regulator of developmental programmed cell death in mammals.

Alleles↗

PubMed1998

Efficient poly A trap approach allows the capture of genes specifically active in differentiated embryonic stem cells and in mouse embryos.

Special vectors have been constructed that allow the trapping of genes in mouse embryonic stem (ES) cells. These vectors generally contain the neomycin phosphotransferase (neo) gene for selection and the beta-galactosidase (beta-gal) gene as a marker. Promoterless vectors can be used to identify genes that are active in undifferentiated ES cells. To also have access to genes that are inactive in totipotent ES cells, we constructed a polyadenylation (poly A) trap vector in which the expression of a poly A less neo gene is driven by a constitutive promoter, whereas the expression of beta-gal depends on the trapped sequences. We demonstrate here that this vector integrates with a high frequency into transcription units and that it traps genes with very different expression patterns in vitro and in vivo. The vector integrates efficiently into transcription units that are inactive in undifferentiated ES cells and which can be activated through in vitro differentiation. Furthermore, in vivo expression patterns demonstrate that this vector integrates into genes that exhibit a highly specific temporal and spatial expression pattern during embryogenesis.

Animals↗

PubMed1995

Disruption of the murine homeobox gene Cdx1 affects axial skeletal identities by altering the mesodermal expression domains of Hox genes.

Cdx1 is expressed along the embryonic axis from day 7.5 postcoitum until day 12, by which time the anterior limit of expression has regressed from the hindbrain level to the forelimb bud region. To assign a functional role for Cdx1 in murine embryonic development, we have inactivated the gene via homologous recombination. Viable fertile homozygous mutant mice were obtained that show anterior homeotic transformations of vertebrae. These abnormalities were concomitant with posterior shifts of Hox gene expression domains in the somitic mesoderm. The presence of putative Cdx1-binding sites in Hox gene control regions as well as in vitro transactivation of Hoxa-7 indicates a direct regulation.

Animals↗

PubMed1993

Mouse Cdx-1 expression during gastrulation.

We describe the expression pattern of the mouse Cdx-1 gene during early development, examined by both RNA and protein analyses. Cdx-1 expression began with the onset of the head process formation (day 7.5) in ectodermal and mesodermal cells of the primitive streak. Expression extended initially to the middle of the prospective hindbrain and subsequently regressed caudad to the spinal cord level by day 9.5. The mesoderm-specific expression was detected in the first somites and could be followed during their differentiation to the myotome of the dorsal somitic edge by day 12. The developing limb buds and the mesonephros exhibited expression up to day 12. No signal could be detected in notochordal cells and cells of the definitive endoderm. Thus, Cdx-1 is expressed during gastrulation when anterior-posterior positional values are established along the embryonic axes. Furthermore, the expression correlates with the formation of segmented tissue in the posterior hindbrain, the spinal cord and structures like the mesonephros.

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