Biomedical subjects

J R Priess

Publications and source records attributed to J R Priess.

34 records · Page 2Linked to original sources

PubMed1996

The PIE-1 protein and germline specification in C. elegans embryos.

Totipotent germline blastomeres in Caenorhabditis elegans contain, but do not respond to, factors that promote somatic differentiation in other embryonic cells. Mutations in the maternal gene pie-1 result in the germline blastomeres adopting somatic cell fates. Here we show that pie-1 encodes a nuclear protein, PIE-1, that is localized to the germline blastomeres throughout early development. During division of each germline blastomere, PIE-1 initially associates with both centrosomes of the mitotic spindle. However, PIE-1 rapidly disappears from the centrosome destined for the somatic daughter, and persists in the centrosome of the daughter that becomes the next germline blastomere. The PIE-1 protein contains potential zinc-finger motifs also found in the mammalian growth-factor response protein TIS-11/NUP475 (refs 4-7). The localization and genetic properties of pie-1 provide an example of a repressor-based mechanism for preserving pluripotency within a stem cell lineage.

Amino Acid Sequence↗

PubMed1996

Repression of gene expression in the embryonic germ lineage of C. elegans.

The distinction between soma and germline was recognized more than a century ago: somatic cells form the body of an organism, whereas germ cells serve to produce future generations. In Caenorhabditis elegans, the separation of some and germline occurs through a series of asymmetrical divisions, in which embryonic germline blastomeres divide unequally to produce one somatic daughter and one germline daughter. Here we show that after each asymmetrical division, embryonically transcribed RNAs are detected in somatic, but not germline, blastomeres. This asymmetry depends on the activity of the germline specific factor, PIE-1. In the absence of PIE-1, embryonically transcribed RNAs are detected in both somatic and germline blastomeres. Furthermore, ectopic expression of PIE-1 in somatic blastomeres can significantly reduce the accumulation of new transcripts in these cells. Taken together, these results suggest that germ-cell fate depends on an inhibitory mechanism that blocks new gene expression in the early embryonic germ lineage.

Animals↗

PubMed1996

par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3.

The generation of asymmetry in the one-cell embryo of Caenorhabditis elegans is necessary to establish the anterior-posterior axis and to ensure the proper identity of early blastomeres. Maternal-effect lethal mutations with a partitioning defective phenotype (par) have identified several genes involved in this process. We have identified a new gene, par-6, which acts in conjunction with other par genes to properly localize cytoplasmic components in the early embryo. The early phenotypes of par-6 embryos include the generation of equal-sized blastomeres, improper localization of P granules and SKN-1 protein, and abnormal second division cleavage patterns. Overall, this phenotype is very similar to that caused by mutations in a previously described gene, par-3. The probable basis for this similarity is revealed by our genetic and immunolocalization results; par-6 acts through par-3 by localizing or maintaining the PAR-3 protein at the cell periphery. In addition, we find that loss-of-function par-6 mutations act as dominant bypass suppressors of loss-of-function mutations in par-2.

Alleles↗

PubMed1996

An inductive interaction in 4-cell stage C. elegans embryos involves APX-1 expression in the signalling cell.

During the 4-cell stage of C. elegans embryogenesis, the P2 blastomere provides a signal that allows two initially equivalent sister blastomeres, called ABa and ABp, to adopt different fates. Preventing P2 signalling in wild-type embryos results in defects in ABp development that are similar to those caused by mutations in the glp-1 and apx-1 genes, which are homologs of the Drosophila genes Notch and Delta, respectively. Previous studies have shown that GLP-1 protein is expressed in 4-cell stage embryos in both ABa and ABp. In this report, we show that APX-1 protein is expressed in the P2 blastomere and that a temperature-sensitive apx-1 mutant has a temperature-sensitive period between the 4-cell and 8-cell stages. We propose that APX-1 is part or all of the P2 signal that induces ABp to adopt a fate different than ABa.

Animals↗

PubMed1995

pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos.

In C. elegans embryogenesis, the MS blastomere produces predominantly mesodermal cell types, while its sister E generates only endodermal tissue. We show that a maternal gene, pop-1, is essential for the specification of MS fate and that a mutation in pop-1 results in MS adopting an E fate. Previous studies have shown that the maternal gene skn-1 is required for both MS and E development and that skn-1 encodes a transcription factor. We show here that the pop-1 gene encodes a protein with an HMG box similar to the HMG boxes in the vertebrate lymphoid-specific transcriptional regulators TCF-1 and LEF-1. We propose that POP-1 and SKN-1 function together in the early embryo to allow MS-specific differentiation.

Amino Acid Sequence↗

PubMed1994

Formation of a monomeric DNA binding domain by Skn-1 bZIP and homeodomain elements.

Maternally expressed Skn-1 protein is required for the correct specification of certain blastomere fates in early Caenorhabditis elegans embryos. Skn-1 contains a basic region similar to those of basic leucine zipper (bZIP) proteins but, paradoxically, it lacks a leucine zipper dimerization segment. Random sequence selection methods were used to show that Skn-1 binds to specific DNA sequences as a monomer. The Skn-1 basic region lies at the carboxyl terminus of an 85-amino acid domain that binds preferentially to a bZIP half-site and also recognizes adjacent 5' AT-rich sequences in the minor groove, apparently with an amino (NH2)-terminal "arm" related to those of homeodomain proteins. The intervening residues appear to stabilize interactions of these two subdomains with DNA. The Skn-1 DNA binding domain thus represents an alternative strategy for promoting binding of a basic region segment recognition helix to its cognate half-site. The results point to an underlying modularity in subdomains within established DNA binding domains.

Amino Acid Sequence↗

PubMed1994

The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo.

The sister blastomeres ABp and ABa are equipotent at the beginning of the 4-cell stage in C. elegans embryos, but soon become committed to different fates. We show that the glp-1 gene, a homolog of the Notch gene of Drosophila, functions in two distinct cell-cell interactions that specify the ABp and ABa fates. These interactions both require maternal expression of glp-1. We show that a second maternal gene, apx-1, functions with glp-1 only in the specification of the ABp fate and that apx-1 can encode a protein homologous to the Delta protein of Drosophila. Our results suggest how interactions mediated by glp-1 and apx-1 contribute to the establishment of the dorsal-ventral axis in the early C. elegans embryo.

Amino Acid Sequence↗

PubMed1994

Establishment of initial asymmetry in early Caenorhabditis elegans embryos.

The Caenorhabditis elegans embryo has anterior/posterior, dorsal/ventral, and left/right axes that correspond to spatially asymmetric patterns of cell differentiation. Recent studies have provided insight into how the different embryonic axes are determined and have shown that the products of the glp-1, skn-1, cap-1, and cap-2 genes appear to be distributed asymmetrically in the early embryo. These gene products should provide important tools for understanding how asymmetries are established initially in nematode embryogenesis.

Animals↗

PubMed1993

The maternal gene skn-1 encodes a protein that is distributed unequally in early C. elegans embryos.

The autonomous or cell-intrinsic developmental properties of early embryonic blastomeres in nematodes are thought to result from the action of maternally provided determinants. After the first cleavage of the C. elegans embryo, only the posterior blastomere, P1, has a cell-intrinsic ability to produce pharyngeal cells. The product of the maternal gene skn-1 is required for P1 to produce pharyngeal cells. We show here that the Skn-1 protein is nuclear localized and that P1 appears to accumulate markedly higher levels of Skn-1 protein than its sister, the AB blastomere. We have examined the distribution of Skn-1 protein in embryos from mothers with maternal-effect mutations in the genes mex-1, par-1, and pie-1. These results suggest that mex-1(+) and par-1(+) activities are required for the unequal distribution of the Skn-1 protein and that pie-1(+) activity may function to regulate the activity of Skn-1 protein in the descendants of the posterior blastomere P1.

Animals↗

PubMed1992

The pie-1 and mex-1 genes and maternal control of blastomere identity in early C. elegans embryos.

During C. elegans embryogenesis an 8-cell stage blastomere, called MS, undergoes a reproducible cleavage pattern, producing pharyngeal cells, body wall muscles, and cell deaths. We show here that maternal-effect mutations in the pie-1 and mex-1 genes cause additional 8-cell stage blastomeres to adopt a fate very similar to that of the wild-type MS blastomere. In pie-1 mutants one additional posterior blastomere adopts an MS-like fate, and in mex-1 mutants four additional anterior blastomeres adopt an MS-like fate. We propose that maternally provided pie-1(+) and mex-1(+) gene products may function in the early embryo to localize or regulate factors that determine the fate of the MS blastomere.

Animals↗

PubMed1992

skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo.

By the 4-cell stage of C. elegans embryogenesis, a ventral blastomere, called EMS, is already committed to producing pharyngeal and intestinal cell types. Recessive, maternal-effect mutations in the gene skn-1 prevent EMS from producing both pharyngeal and intestinal cells. In skn-1 mutant embryos, EMS instead produces hypodermal cells and body wall muscle cells, much like its sister blastomere. Genetic analysis suggests that the skn-1 gene product is also required post-embryonically for development of the intestine. We have cloned and sequenced the skn-1 gene and describe sequence similarities to the basic regions of bZIP transcription factors. We propose that the maternally expressed skn-1 gene product acts to specify the fate of the EMS blastomere.

Amino Acid Sequence↗

PubMed1992

Cell interactions involved in development of the bilaterally symmetrical intestinal valve cells during embryogenesis in Caenorhabditis elegans.

We describe two different cell interactions that appear to be required for the proper development of a pair of bilaterally symmetrical cells in Caenorhabditis elegans called the intestinal valve cells. Previous experiments have shown that at the beginning of the 4-cell stage of embryogenesis, two sister blastomeres called ABa and ABp are equivalent in development potential. We show that cell interactions between ABp and a neighboring 4-cell-stage blastomere called P2 distinguish the fates of ABa and ABp by inducing descendants of ABp to produce the intestinal valve cells, a cell type not made by ABa. A second cell interaction appears to occur later in embryogenesis when two bilaterally symmetrical descendants of ABp, which both have the potential to produce valve cells, contact each other; production of the valve cells subsequently becomes limited to only one of the two descendants. This second interaction does not occur properly if the two symmetrical descendants of ABp are prevented from contacting each other. Thus the development of the intestinal valve cells appears to require both an early cell interaction that establishes a bilaterally symmetrical pattern of cell fate and a later interaction that breaks the symmetrical cell fate pattern by restricting to only one of two cells the ability to produce a pair of valve cells.

Animals↗

PubMed1988

Identification of genes required for cytoplasmic localization in early C. elegans embryos.

We have isolated and analyzed eight strict maternal effect mutations identifying four genes, par-1, par-2, par-3, and par-4, required for cytoplasmic localization in early embryos of the nematode C. elegans. Mutations in these genes lead to defects in cleavage patterns, timing of cleavages, and localization of germ line-specific P granules. Four mutations in par-1 and par-4 are fully expressed maternal effect lethal mutations; all embryos from mothers homozygous for these mutations arrest as amorphous masses of differentiated cells but are specifically lacking intestinal cells. Four mutations in par-2, par-3, and par-4 are incompletely expressed maternal effect lethal mutations and are also grandchildless; some embryos from homozygous mothers survive and grow to become infertile adults due to absence of functional germ cells. We propose that all of these defects result from the failure of a maternally encoded system for intracellular localization in early embryos.

Animals↗

PubMed1987

The glp-1 locus and cellular interactions in early C. elegans embryos.

Interactions between the early blastomeres in a C. elegans embryo are required for the specification of certain cell fates. Blastomeres that produce neurons and skin cells when cultured in isolation are induced to also produce pharyngeal cells in intact embryos. We have identified maternal effect lethal mutations that, on the basis of phenotype and temperature-sensitive period, appear to disrupt this inductive interaction. These mutations are all alleles of glp-1, a gene also involved in the control of germ cell proliferation during postembryonic development of C. elegans.

Alleles↗

PubMed1987

Cellular interactions in early C. elegans embryos.

In normal development both the anterior and posterior blastomeres in a 2-cell C. elegans embryo produce some descendants that become muscles. We show that cellular interactions appear to be necessary in order for the anterior blastomere to produce these muscles. The anterior blastomere does not produce any muscle descendants after either the posterior blastomere or one of the daughters of the posterior blastomere is removed from the egg. Moreover, we demonstrate that a daughter of the anterior blastomere that normally does not produce muscles appears capable of generating muscles when interchanged with its sister, a cell that normally does produce muscles. Embryos develop normally after these blastomeres are interchanged, suggesting that cellular interactions play a major role in determining the fates of some cells in early embryogenesis.

Animals↗

PubMed1986

Caenorhabditis elegans morphogenesis: the role of the cytoskeleton in elongation of the embryo.

During development Caenorhabditis elegans changes from an embryo that is relatively spherical in shape to a long thin worm. This paper provides evidence that the elongation of the body is caused by the outermost layer of embryonic cells, the hypodermis, squeezing the embryo circumferentially. The hypodermal cells surround the embryo and are linked together by cellular junctions. Numerous circumferentially oriented bundles of microfilaments are present at the outer surfaces of the hypodermal cells as the embryo elongates. Elongation is associated with an apparent pressure on the internal cells of the embryo, and cytochalasin D reversibly inhibits both elongation and the increase in pressure. Circumferentially oriented microtubules also are associated with the outer membranes of the hypodermal cells during elongation. Experiments with the microtubule inhibitors colcemid, griseofulvin, and nocodazole suggest that the microtubules function to distribute across the membrane stresses resulting from microfilament contraction, such that the embryo decreases in circumference uniformly during elongation. While the cytoskeletal organization of the hypodermal cells appears to determine the shape of the embryo during elongation, an extracellular cuticle appears to maintain the body shape after elongation.

Actin Cytoskeleton↗