Section IIntroduction

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The body plan of the Caenorhabditis elegans embryo is established during the first few cleavages. The reproducible orientations of these cleavages coupled with asymmetric localization of cytoplasmic components initiate processes that establish the three principal axes of the body and set the fates of the six founder cells. In this chapter, we review the current understanding of mechanisms controlling the early cleavages, and we address the following issues: (1) when and how embryonic polarity is established, (2) how cytoplasmic factors are differentially partitioned along an axis, and (3) how spindle positioning is controlled to generate cells of the correct sizes, in the correct positions, and with the correct contents.

A. Overview of Embryogenesis

For detailed descriptions of C. elegans embryogenesis, see Sulston et al. (1983), which describes the entire embryonic lineage, and Wood (1988) and Strome (1989). It takes 14 hours at 20°C for a newly fertilized embryo to complete embryogenesis and hatch from its eggshell into a juvenile worm. During the first few hours, the embryo undergoes a series of four unequal divisions, to produce five somatic founder cells (AB, E, MS, C, and D) and the primordial germ cell (P4) by the 28-cell stage (Figs. 1 and 2a–i). Gastrulation begins at the 28-cell stage when the two daughters of E move to the interior of the embryo (Fig. 2i), followed later by P4 and some of the descendants of MS, C, D, and AB. These cell movements, coupled with continued proliferation, result in a generally triploblastic embryo of 300 cells, with an internal cylinder of pharynx and gut primordia, an outer layer of hypodermal and neuronal precursors, and four quadrants of body wall myoblasts between the two layers. Cell divisions cease when the embryo contains 550 cells (Fig. 3). During the second half of embryogenesis, tissues differentiate and become more highly organized and separated from each other, and the spherical embryo is squeezed by circumferential microfilaments and microtubules into a vermiform worm (Figs. 2j–l and 3).

Figure 1. Early cell lineage tree.

Figure 1

Early cell lineage tree. Cell divisions are indicated by horizontal lines; the anterior daughter of each division is placed on the left. A series of unequal divisions of the germ-line or P cells results (more...)

Figure 2. Nomarski differential interference-contrast images of living embryos.

Figure 2

Nomarski differential interference-contrast images of living embryos. Anterior is left, and ventral is down. (a) Appearance of the oocyte (o) and sperm (s) pronuclei; (b) (more...)

Figure 3. Summary of events in embryogenesis.

Figure 3

Summary of events in embryogenesis. The timing of key events and stages of elongation (at 20°C) are shown on the left. The number of living nuclei in different stage embryos is plotted on (more...)

B. Overview of Early Embryonic Polarity

Figure 4 summarizes known anterior-posterior (A-P) asymmetries of the early embryo (also see Goldstein et al. 1993). The unfertilized oocyte shows no asymmetry other than the eccentric placement of the egg nucleus and the presence of a cytoplasmic bridge linking each oocyte to the common cytoplasm of the germ line (Strome 1986a; White 1988). During the first cell cycle, however, the zygote becomes discernibly polarized along its long axis. The first cleavage bisects this axis, producing two daughter cells of different sizes with different developmental potentials (Laufer et al. 1980; Cowan and Macintosh 1985; Priess and Thomson 1987). The blastomeres also differ in cell division timing, centrosome behavior, and cytoplasmic composition.

P granules are perhaps the best known marker of early embryonic polarity (Strome and Wood 1982, 1983). These granules are present in the cytoplasm of oocytes and early embryos, become localized to the posterior of the zygote, and are partitioned to the posterior blastomere, P1. They continue to be partitioned asymmetrically at each of the unequal cleavages in the germ-line cells (P1, P2, and P3) and remain associated with the germ lineage throughout the life of the worm. Because of their polar distribution and their association with the germ line, it is possible that they play a part in establishing embryonic polarity or germ-cell fate or both. P granules appear to be ribonucleoprotein particles. In situ hybridization studies have shown that P granules are associated with SL1-containing, poly(A)+ RNAs (Seydoux and Fire 1994). In addition to unidentified proteins that are recognized by monoclonal antibodies (Strome and Wood 1983; Yamaguchi et al. 1983), two known proteins, GLH-1, a putative RNA helicase, and MEX-3, a protein with putative RNA-binding domains, have been detected in P granules by immunolocalization studies (Roussell and Bennett 1993; M. Gruidl and K. Bennett; B. Draper and J. Priess, both pers. comm.). PGL-1, a novel protein with a putative RNA-binding domain, may be another component of P granules. pgl-1 mutant worms lack some P-granule epitopes and show a maternal-effect sterile phenotype (I. Kawasaki, and S. Strome, unpubl.). This is consistent with the notion that P granules are indeed involved in some aspect of germ-line development.

Important developmental regulators also exhibit asymmetric distributions in early embryos: SKN-1 (Bowerman et al. 1993), GLP-1 (Evans et al. 1994), PIE-1 (C. Mello et al., pers. comm.), and PAL-1 (C. Hunter and C. Kenyon, pers. comm.). SKN-1, PIE-1, and PAL-1 are localized to posterior cells via unknown mechanisms. GLP-1 is detected in only the anterior cell, AB, and its immediate descendants and is restricted to these cells by translational control (Evans et al. 1994).

Some maternal messenger RNAs are also asymmetrically distributed in early embryos. In most cases, the differences are due to differential mRNA stability in germ-line versus somatic cells (Seydoux and Fire 1994), but two cases of mRNAs with graded distributions in one-cell embryos have been reported ( pos-1 , H. Tabara et al., pers. comm.; mex-3 , B. Draper and J. Priess, pers. comm.).

The roles of some of these localized molecules are discussed in Schnabel and Priess (this volume). In the remainder of this chapter, we provide a more detailed description of the events of early embryogenesis and review progress toward understanding the mechanisms responsible for establishing polarity.