Genetic Control of Cellular Interactions in Caenorhabditis Elegans Development

Author(s):  
Judith Kimble ◽  
Judith Austin
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.


2003 ◽  
Vol 358 (1436) ◽  
pp. 1313-1315 ◽  
Author(s):  
R. L. Gardner ◽  
M. A. Surani ◽  
D. Solter

The elaboration of a physiologically integrated organism from a fertilized egg depends on processes of cellular growth and diversification that require very precise coordination in both space and time. The extent to which the final outcome is presaged in the egg is an issue that has engaged those seeking to explain embryonic development since antiquity. According to the concept of preformation espoused by Charles Bonnet, the new organism was already present in its final form in the egg, so that development simply entailed enlargement without any accompanying increase in complexity (Oppenheimer 1967). This extreme view was shown to be untenable by Caspar Friedrich Wolff, whose relevant studies included careful documentation of the emergence of increasingly complex organization during the course of embryogenesis in the chick. As a result, the opposing concept of epigenesis, namely that order and form emerge de novo during the course of development, rapidly gained dominance (Oppenheimer 1967). However, by the latter half of the nineteenth century, preformation was revived in a subtler guise to explain the development of various marine invertebrates in which both patterns of cleavage and differentiation of the resulting blastomeres were essentially invariant. Here, cellular diversification was attributed to the localization within the cytoplasm of the egg of factors, or ‘determinants’, which dictated the fate of the cells that inherited them. The stereotypical pattern of cleavage exhibited by such organisms was referred to as ‘mosaic’, in contrast to the variable or ‘regulative’ pattern shown by many others. Mosaic soon came to be equated with a determinant–based or neo–preformationist, and regulative with an epigenetic, view of development. We now know that this distinction is not valid because cellular interactions play a vital part in the development even of organisms with invariant lineage like Caenorhabditis elegans, whereas ‘determinants’ such as those for the germline occur in species whose lineage is variable.


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.


The nematode Caenorhabditis elegans normally exists as one of two sexes: self-fertilizing hermaphrodite or male. Development as hermaphrodite or male requires the differentiation of each tissue in a sex-specific way. In this review, I discuss the genetic control of sex determination in a single tissue of C. elegans : the germ line. Sex determination in the germ line depends on the action of two types of genes: - those that act globally in all tissues to direct male or female development and those that act only in the germ line to specify either spermatogenesis or oogenesis. First, I consider a tissue-specific sex-determining gene, fog-1 , which promotes spermatogenesis in the germ line. Second, I consider the regulation of the hermaphrodite pattern of germ ­ line gametogenesis where first sperm and then oocytes are produced.


The genetic control of cell lineage has been studied extensively in Caenorhabditis elegans . In this paper, three studies of cell lineage mutants are reviewed: the isolation of mutations affecting vulval cell lineages, and the analysis of two ‘control genes’, lin -12 and lin -14. In addition, certain logical features of the genetic programme, as inferred from or illuminated by the study of cell lineage mutants, are discussed: the concepts of ‘ control genes ’ and developmental subprogrammes, and the organization of the lineage into a hierarchy of binary decisions.


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