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Insights into morphogenesis from a simple developmental system

Key Points

  • Dictyostelium discoideum development is initiated by starvation, which induces chemotaxis of individual cells into an aggregate that produces an organism consisting of around 100,000 cells.

  • Differentiation into two main cell types, prestalk and prespore cells, is initially based on the phase of the cell cycle that individual cells were in when nutrients were exhausted, but can be subsequently modified and is regulated by additional signals. For example, the morphogens cyclic AMP and differentiation-inducing factor-1 (DIF-1) facilitate prespore and prestalk cell distribution, respectively, and a Wnt-like pathway induces prespore differentiation through activation of glycogen-synthase kinase-3 (GSK3).

  • Cell migration within the aggregate is responsible for the initial sorting of prestalk cells to the tip of the aggregate and then for subsequent morphogenesis. The mechanisms of directed cell movement that are responsible for the migration of single cells to form the initial aggregate are also responsible for movement in the context of the multicellular tissue.

  • The reciprocal transient localization and activation of phosphatidylinositol 3-kinase (PI3K) and the phosphatase and tensin homologue (PTEN) establishes the polarity of cells responding to chemotactic signals and leads to regulation of actin polymerization in the leading edge and myosin-II assembly in the lateral cortex.

  • Control of cortical tension, which is mediated by myosin II and actin-associated proteins, is important for migration of cells in the context of a three-dimensional tissue. Myosin-II mutants are unable to resist the forces that are produced by cell–cell adhesion.

  • Chimeric organisms, which can easily be produced by co-aggregating two different D. discoideum strains such as green fluorescent protein (GFP)-tagged mutants or fluorescently marked prespore or prestalk cells, provide a means of directly testing the role of migration and adhesion in specific aspects of morphogenesis.

Abstract

We are only starting to understand the molecular mechanisms that underlie cell and tissue movements during morphogenesis in metazoans. Dictyostelium discoideum provides a valuable model system for understanding these events — as it has for chemotaxis — despite the many differences that exist between this social amoeba and more complex organisms. Genetic and genomic studies, combined with real-time imaging, have identified key pathways that regulate morphogenesis in D. discoideum, and which are likely to have similar roles in metazoans.

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Figure 1: Dictyostelium discoideum morphogenesis.
Figure 2: Sorting of differentiating cells within the mound.
Figure 3: Pattern formation in fingers, slugs and early culminants.
Figure 4: The fruiting body or culminant.
Figure 5: Spatial localization of signalling components that are required for cell polarization and chemotaxis in Dictyostelium discoideum.
Figure 6: Regulation of the prestalk pathway.
Figure 7: A comparison of GSK3 signalling pathways and regulation of developmental fate choice in D. discoideum, mammals and C. elegans.

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Acknowledgements

We are indebted to the D. discoideum community at large who supplied essential information for compiling the data that is presented in the table of developmental mutants (see online links box). We also acknowledge the key work by Petra P. Fey and P. Gaudet at dictyBase (http://dictybase.org/) in establishing this resource. We are indebted to A. Kimmel (National Institutes of Health) and J. Williams (University of Dundee) for supplying the outlines of figures for the D. discoideum Wnt-like and STAT pathways.

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DATABASES

Dictybase

abpC

cadA

carA

carC

carD

CsaA

CudA

dagA

dstC

erkB

Gα2

gbfA

gskA

LagC

limB

mhcA

mlcR

PAKa

PhdA

pkbA

pkgB

ptenA

racB

RegA

scrA

TalB

UbcB

UbpB

zakA

FURTHER INFORMATION

Tutorial website

Table of developmental mutants

Signalling website

Glossary

YOLK-SAC CELLS

Cells within the yolk sac of a developing vertebrate embryo.

NEURAL CREST CELLS

Cells that originate from the neural crest region of a vertebrate embryo. They migrate outward and are progenitors of mature cell types, including peripheral neurons.

LASER ABLATION

Destruction of a cell in a living embryo using a laser.

FRUITING BODY

The final structure of a D. discoideum organism.

EMBRYONIC ORGANIZER

The regions within an embryo that control development and differentiation.

CULMINANT

The mature, or maturing, terminally-differentiated structure of a D. discoideum organism.

AGGREGATION CENTRES

Signal regions in the centre of a D. discoideum aggregation domain that are the origin of the outward-moving chemoattractant signalling wave.

PHOTOTAXIS

The movement of a cell towards a source of light.

THERMOTAXIS

The movement of a cell towards a source of temperature.

LEADING EDGE

The leading, or foremost, region of a motile cell.

LAMELLIPODIUM

A thin, flat extension at the cell periphery that is filled with a branching meshwork of actin filaments.

PSEUDOPODIUM

A temporary projection of the cytoplasm of certain cells, such as neutrophils, or of certain unicellular organisms, especially amoebae, that functions in locomotion.

MYOSIN-II FILAMENTS

Filaments of assembled head-to-tail myosin-II dimers that mediate intracellular contractility.

PLECKSTRIN HOMOLOGY (PH) DOMAIN

A sequence of 100 amino acids that is present in many signalling molecules and binds to lipid products of phosphatidylinositol 3-kinase. Pleckstrin is a protein of unknown function that was originally identified in platelets. It is a principal substrate of protein kinase C.

F-BOX MOTIF

A protein motif of approximately 50 amino acids that facilitates protein–protein interactions. F-box proteins confer substrate specificity on an invariant core ubiquitylation complex.

WD40 REPEAT

A repeat of 40 amino acids with a characteristic central Trp-Asp motif. Similar to those of the Gβ subunit of heterotrimeric G proteins, these repeats are often associated with an F-box motif.

DOMINANT-NEGATIVE

A defective protein that retains interaction capabilities and so distorts or competes with normal proteins.

MOSAIC-ANALYSIS EXPERIMENTS

Experiments in which an organism has cells with two different mutant backgrounds. Often used to examine cell automony of mutant phenotypes.

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Chisholm, R., Firtel, R. Insights into morphogenesis from a simple developmental system. Nat Rev Mol Cell Biol 5, 531–541 (2004). https://doi.org/10.1038/nrm1427

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