lin-12 and glp-1 are required zygotically for early embryonic cellular interactions and are regulated by maternal GLP-1 signaling in Caenorhabditis elegans

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 4105-4117 ◽  
Author(s):  
I.P. Moskowitz ◽  
J.H. Rothman

Cell-cell interactions mediated by LIN-12 and GLP-1, members of the LNG (LIN-12, Notch, GLP-1) family of receptors, are required to specify numerous cell fates during development of the nematode Caenorhabditis elegans. Maternally expressed GLP-1 participates in two of at least four sequential inductive interactions that specify the fates of early embryonic descendants of the AB founder cell. We report that GLP-1 and LIN-12, and apparently their ligand, LAG-2, as well as a downstream component, LAG-1, are required in the latter two inductions. We find that LAG-2 is expressed in the signaling cells and LIN-12 is expressed in cells receiving the inductions, consistent with their proposed roles as ligand and receptor, respectively. Furthermore, we report that maternal GLP-1 activity is required (1) to repress early zygotic lag-2 expression and (2) to activate zygotic lin-12 expression in the early embryo. The patterning of both receptor and ligand expression by maternal GLP-1 signaling establishes competence for the zygotic LNG-mediated cellular interactions and localizes these interactions to the appropriate cells. We propose that activation of maternal GLP-1 regulates zygotic lin-12 and lag-2 expression by a regulatory mechanism analogous to that described for the post-embryonic gonad.

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2219-2232 ◽  
Author(s):  
R. Schnabel

During the first four cleavage rounds of the Caenorhabditis elegans embryo, five somatic founder cells AB, MS, E, C and D are born, which later form the tissues of the embryo. The classical criterion for a cell-autonomous specification of a tissue is the capability of primordial cells to produce this tissue in isolation from the remainder of the embryo. By this criterion, the somatic founder cells MS, C and D develop cell-autonomously. Laser ablation experiments, however, reveal that within the embryonic context these blastomeres form a network of duelling cellular interactions. During normal development, the blastomere D inhibits muscle specification in the MS and the C lineage inhibits muscle specification in the D lineage. These inhibitory interactions are counteracted by two activating inductions. As described before the inhibition of body wall muscle in MS is counteracted by an activating signal from the ABa lineage. Body wall muscle in the D lineage is induced by MS descendants, which suppress an inhibitory activity of the C lineage. The interaction between the D and the MS lineage occurs through the C lineage. An interesting feature of these cell-cell interactions is that they do not serve to discriminate between equivalent cells but are permissive or nonpermissive inductions. No evidence was found that the C-derived body wall muscle also depends on an induction, which suggests that possibly three different pathways coexist in the early embryo to specify body wall muscle, two of which are, in different ways, influenced by cell-cell interactions and a third that is autonomous. This work supplies evidence that cells may acquire transient states during embryogenesis that influence the specification of other cells in the embryo. These states, however, may not be reflected in the developmental potentials of the cells themselves. They can only be scored indirectly by their action on the specification of other cells in the embryo. Blastomeres that behave cell-autonomously in isolation are nevertheless subjected to cell-cell interactions in the embryonic context. Why this should be is an intriguing question. The classical notion has been that blastomeres are specified autonomously in nematodes. In recent years, it was established that at least five inductions are required to determine the AB descendants of C. elegans, whereas the P1 descendants have been typically viewed to develop more autonomously. It appears now that inductions also play a major role during the determination of P1-derived blastomeres.


2004 ◽  
Vol 15 (6) ◽  
pp. 2782-2793 ◽  
Author(s):  
Kanako Ono ◽  
Shoichiro Ono

Ovulation in the nematode Caenorhabditis elegans is coordinated by interactions between the somatic gonad and germ cells. Myoepithelial sheath cells of the proximal ovary are smooth muscle-like cells, but the regulatory mechanism of their contraction is unknown. We show that contraction of the ovarian muscle requires tropomyosin and troponin, which are generally major actin-linked regulators of contraction of striated muscle. RNA interference of tropomyosin or troponin C caused sterility by inhibiting ovarian contraction that is required for expelling mature oocytes into the spermatheca where fertilization takes place, thus causing accumulation of endomitotic oocytes in the ovary. Tropomyosin and troponin C were associated with actin filaments in the myoepithelial sheath, and the association of troponin C with actin was dependent on tropomyosin. A mutation in the actin depolymerizing factor/cofilin gene suppressed the ovulation defects by RNA interference of tropomyosin or troponin C. These results strongly suggest that tropomyosin and troponin are the actin-linked regulators for contraction of ovarian muscle in the C. elegans reproductive system.


Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 53-57
Author(s):  
Judith Austin ◽  
Eleanor M. Maine ◽  
Judith Kimble

Cell–cell interactions play a significant role in controlling cell fate during development of the nematode Caenorhabditis elegans. It has been found that two genes, glp-1 and lin-12, are required for many of these decisions, glp-1 is required for induction of mitotic proliferation in the germline by the somatic distal tip cell and for induction of the anterior pharynx early in embryogenesis. lin-12 is required for the interactions between cells of equivalent developmental potential, which allow them to take on different fates. Comparison of these two genes on a molecular level indicates that they are similar in sequence and organization, suggesting that the mechanisms of these two different sets of cell–cell interactions are similar.


Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3325-3338 ◽  
Author(s):  
I.P. Moskowitz ◽  
S.B. Gendreau ◽  
J.H. Rothman

Most somatic cells in the nematode Caenorhabditis elegans arise from AB, the anterior blastomere of the 2-cell embryo. While the daughters of AB, ABa and ABp, are equivalent in potential at birth, they adopt different fates as a result of their unique positions. One such difference is that the distribution of epidermal precursors arising from ABp is reversed along the anterior-posterior axis relative to those arising from ABa. We have found that a strong mutation in the glp-1 gene eliminates this ABa/ABp difference. Furthermore, extensive cell lineage analyses showed that ABp adopts an ABa-like fate in this mutant. This suggests that glp-1 acts in a cellular interaction that makes ABp distinct from ABa. One ABp-specific cell type was previously shown to be induced by an interaction with a neighboring cell, P2. By removing P2 from early embryos, we have found that the widespread differences between ABa and ABp arise from induction of the entire ABp fate by P2. Lineage analyses of genetically and physically manipulated embryos further suggest that the identifies of the AB great-granddaughters (AB8 cells) are controlled by three regulatory inputs that act in various combinations. These inputs are: (1) induction of the ABp-specific fate by P2, (2) a previously described induction of particular AB8 cells by a cell called MS, and (3) a process that controls whether an AB8 cell is an epidermal precursor in the absence of either induction. When an AB8 cell is caused to receive a new combination of these regulatory inputs, its lineage pattern is transformed to resemble the lineage of the wild-type AB8 cell normally receiving that combination of inputs. These lineage patterns are faithfully reproduced irrespective of position in the embryo, suggesting that each combination of regulatory inputs directs a unique lineage program that is intrinsic to each AB8 cell.


Development ◽  
1986 ◽  
Vol 97 (Supplement) ◽  
pp. 15-29
Author(s):  
Susan Strome

One of the central problems facing developmental biologists is understanding how the unicellular zygote develops into a multicellular embryo composed of different tissue types. It is now clear that differentiated cell types differ because they express different sets of genes. However, how cells become instructed to express different sets of genes remains a mystery. One popular model for how cell fates are determined invokes the existence and asymmetric distribution of cytoplasmic ‘determinants’ of cell fates (for reviews see Wilson, 1925; Davidson, 1976). According to this model, the developmental programmes of embryonic blastomeres are specified by internal factors that are differentially segregated to different blastomeres during the early cleavages of the zygote. Alternatively, cells may be instructed by extrinsic signals, in which case the positions of cells in the embryo and cell-cell interactions would be important. Observation and manipulation of embryos that show ‘mosaic’ development provide indirect support for the cell determinant theory.


Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 253-259 ◽  
Author(s):  
M.A. Felix ◽  
P.W. Sternberg

How do intercellular signals that pattern cell fates vary in evolution? During nematode vulva development, precursor cells acquire one of three fates in a pattern centered around the gonadal anchor cell. Non-vulval fates are at the periphery, outer and inner vulval fates are towards the center. In Caenorhabditis elegans, the three fates are specified around the same time by an induction by the anchor cell and lateral signaling between the vulva precursor cells. We find that, in three other nematode species (Panagrolaimus, Oscheius and Rhabditella spp.) spanning two families, the centered pattern is obtained by two temporally distinct gonadal inductions. The first induction specifies vulval fates; the second induction specifies the inner vulval fates in a subset of the precursors' daughters. This evolutionary change in the spatiotemporal connectivity of cell interactions allows centering of the pattern between two precursors in Panagrolaimus.


Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4759-4767 ◽  
Author(s):  
C. Wen ◽  
M.M. Metzstein ◽  
I. Greenwald

LIN-12/NOTCH proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.


Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2481-2492
Author(s):  
C. Goutte ◽  
W. Hepler ◽  
K.M. Mickey ◽  
J.R. Priess

In animal development, numerous cell-cell interactions are mediated by the GLP-1/LIN-12/NOTCH family of transmembrane receptors. These proteins function in a signaling pathway that appears to be conserved from nematodes to humans. We show here that the aph-2 gene is a new component of the GLP-1 signaling pathway in the early Caenorhabditis elegans embryo, and that proteins with sequence similarity to the APH-2 protein are found in Drosophila and vertebrates. During the GLP-1-mediated cell interactions in the C. elegans embryo, APH-2 is associated with the cell surfaces of both the signaling, and the responding, blastomeres. Analysis of chimeric embryos that are composed of aph-2(+) and aph-2(−) blastomeres suggests that aph-2(+) function may be provided by either the signaling or responding blastomere.


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