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Gastrulation: Partaking of the Bottle Dispatch

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Gastrulation: Partaking of the Bottle Dispatch Current Biology, Vol. 13, R223–R225, March 18, 2003, ©2003 Elsevier Science Ltd. All rights reserved. DOI 10.1016/S0960-9822(03)00155-6 Gastrulation: PARtaking of the Bottle Dispatch Aaron P. Putzke and Joel H. Rothman constriction of their apical ends, resulting in bending of the sheet and their inward movement toward the opposite (basal) surface. The mechanics of such apical Gastrulation in C. elegans embryos involves constriction was modeled over 55 years ago [8] with ingression of individual cells, but is driven by apical brass bars and rubber bands representing a layer of constriction of the kind that promotes migration of epithelial cells: by changing the tension on one side of epithelial cell sheets. Recent work shows that PAR the layer, the sheet would buckle inward, thus mimick- proteins, known for their role in polarization and ing ingression. unequal cell division, are also associated with the Ingression by apical constriction may be energeti- polarization that establishes this apical constriction. cally more favorable than other means of gap closure, such as the purse-string model. A study using com- puter algorithms to mimic gastrulating embryos showed How poor are they who have not gastrulation! that, when a cell constricts apically, it propagates a What wound did ever heal but by ingression? wave through the surrounding sheet of cells, causing (apologies to William Shakespeare) an inward buckling [9]. Morphological support for apical constriction in a developing organism came from the observation of bottle cells, for example during We all begin as a cluster of rather featureless cells; our primary invagination of epithelial cells in sea urchins final forms are sculpted into specialized tissue layers [1], in which bottle cells have been shown to be essen- which achieve their final state by the concerted move- tial for gastrulation [2]. Moreover, molecular evidence ments of cells. In triploblastic animals, multiple layers for apical constriction has been reported in Drosophila, initially arise from a cluster of cells by ingression or in which it was found that actin and myosin localize to gastrulation, a process that has attracted the attention apical cortices, concomitant with cell shape changes of developmental biologists since His proposed in during ventral furrow formation [10,11]. 1874 that invagination is propagated by forces arising The simplicity of C. elegans gastrulation, which from cell division [1]. Although gastrulation looks begins with the ingression of just two cells — the gut dramatically different in various beasts — such as precursor cells or ‘endoderm pair’ (Figure 1A) — makes echinoderms [2], insects [3] and vertebrates [4] (Figure it a highly manipulable system with which to study the 1A) — it generally involves the coordinated inward mechanisms that drive cell ingression (with the caveat movement of epithelialized cell sheets. But some that one must suffer an onslaught of jokes from epithe- creatures, such as nematodes, present an extreme liocentric researchers, who would have us believe that case of simplicity in which ingression of individual, what these worm embryos do is not truly ‘gastrula- rather than sheets, of cells sink into the embryonic tion’). It has been suggested that proper cell contacts interior apparently independently during gastrulation. are essential for gastrulation in C. elegans [12], imply- Recent studies on embryos of the nematode ing that interactions between ingressing cells and their Caenorhabditis elegans indicate that the cellular mech- neighbors are essential for this movement. It was anisms promoting ingression may be common to recently shown, however, that gastrulation movements animals with widely divergent modes of gastrulation. A of the endoderm pair can occur in culture with a small common theme in gastrulation is that invaginating cells number of cells, and that cell-autonomous apical con- constrict at their apical ends, resulting in wedge-shape striction of these two cells drives their inward migration ‘bottle cells’. Cell autonomous apical constriction [5], [5]. Such a cell-autonomous mechanism may also triggered by cell-fate specification [6], has recently occur during Drosophila gastrulation where, prior to been found also to drive gastrulation in C. elegans. ingression, the apical constriction of ventral cells Unexpectedly, the ‘PAR’ proteins, known from their occurs stochastically, perhaps suggesting that cell role in generating the anterior-posterior cell polarity contacts may not be necessary for apical constriction that creates unequal daughters during asymmetric to take place [3]. cleavage of the zygote, are also implicated in the As in other animals, microfilaments — but not micro- apical-basal asymmetry of ingressing cells [6]. tubules — are essential for gastrulation in C. elegans. One model describing the mechanisms of cell A non-muscle myosin localizes to the apical edges of ingression during gastrulation posits that cells adjacent the ingressing endoderm cells, and pharmacological to ingressing cells move toward the site of internaliza- studies suggest that myosin activity is required for tion, causing the cell sheet to buckle [7]. Another gastrulation [5], further demonstrating the importance popular view proposes that a continuous actomyosin of the actomyosin system in nematode gastrulation. ‘purse-string’ within a ring of cells contracts, causing But active migration of cells surrounding the ingress- cells within the ring to ingress. In the most commonly ing cells is not essential for their movement into the held model, ingressing cells change their shape by interior. At the time of their ingression, the pair of endo- derm cells is flanked on the anterior and posterior Department of MCD Biology, University of California, Santa sides, respectively, by a mesodermal and a germline Barbara, California 93106, USA. progenitor (Figure 1A); these flanking cells congress to E-mail: [email protected] fill the gap left on the surface following migration of the Dispatch R224 Figure 1. Gastrulation movements and A changes in PAR protein localization. (A) Gastrulation events in three model organisms: lateral view of a sea urchin embryo with ingression of bottle cells (wedge-shaped cells); ventral furrow for- mation in Drosophila (ingressing cells shaded gray); and lateral view of C. Ea Ep P4 elegans embryo. The intestinal precursor MS cells — the ‘endoderm pair’ Ea and Ep — ingress, while mesoderm (MS) and germline (P4) descendants move to overlie Ea and Ep. (Black arrows indicate movement of ingressing cells.) (B) Local- B ization of PAR-2 (red) and PAR-3 (green) in C. elegans two-cell and 26-cell embryos, respectively. In two-cell embryos, PAR-3 excludes PAR-2 from the AB P1 anterior of P1. In the 26-cell embryos, PAR-3 and PAR-2 have switched from anterior-posterior polarity to apical-basal polarity (shown here only for the endo- derm pair). PAR-3 excludes PAR-2 from Current Biology the apical surface of each cell. ingressing cells. The flanking cells do not move example, the twist gene, which is expressed in the together by chemotaxis or by actively undergoing pro- ventralmost cells of the fly embryo prior to ventral trusion-based motility during ingression of the endo- furrow formation, is required to specify mesodermal derm pair [5]. Rather, apical constriction of the cell fate and gastrulation. In the absence of Twist ingressing endoderm cells — which has been detected protein, ingression and the subsequent differentiation by observing the convergence of fluorescent micros- of ventral cells do not occur. pheres adhering to their surfaces — apparently draws While the machinery that drives gastrulation in C. the flanking cells towards each other, as the endoderm elegans is not well understood, a possible link has cells shrink away from the embryonic surface [5]. The been made between proteins that direct asymmetric polarity that results in apical constriction of the endo- cell division and the asymmetric behavior of derm pair is an intrinsic property of these cells, as the ingressing cells in C. elegans [6]. The PAR proteins position of the flanking cells does not alter this polarity. were originally identified by their requirement in A number of studies have shown that, in C. elegans, establishing cell polarity and directing asymmetric cell cells are specified before they are sent into the interior divisions in C. elegans, and orthologs have since been of the embryo, and that gastrulation requires proper shown to function in cell polarity in Drosophila, cell-fate specification. For example, inhibition of zygotic Xenopus and mammals. PAR-3 and PAR-6 localize at transcription blocks ingression of the endoderm pair the anterior cortex of the dividing zygote, and PAR-2 [13], as do mutations in a number of maternal and is reciprocally localized at the posterior cortex [18]. zygotic genes that are essential for specifying the iden- This reciprocal localization shifts from anterior-poste- tity of the endoderm progenitor cell [14]. Specification rior to apical-basal polarity after the two-cell stage of cells as mesodermal is sufficient to activate their (Figure 1B) [6]. ingression: a mutation that transforms ectodermal Asymmetric PAR protein localization at the cortex progenitors, which do not normally ingress, into meso- depends on cell contact: PAR-2 localizes to regions dermal precursors, confers the potential to undergo where cells are in contact, whereas PAR-3 and PAR–6 ectopic ingression [6]. are present in regions that are not in
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