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Cell-cell adhesion and signal transduction during Dictyostelium development

¹ MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower Street, London, WC1E 6BT, UK
² Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge, CB2 3EA, UK

View larger version (14K): [in a new window]   Fig. 1. Dictyostelium development. Amoebae proliferate as single cells during the growth phase. Upon starvation, amoebae undergo chemotaxis towards a pulsatile cyclic AMP (cAMP) source. During aggregation, cells coalesce into adherent cell ‘streams’ that eventually come together to form the mound, the first stage of multicellular development. The mound compacts to form a tight aggregate and then develops a ‘tip’, which coordinates further development. After extension to form the first finger, the developing structure either immediately forms a fruiting body, the process of culmination or forms a motile slug that migrates to seek conditions favourable for culmination. Scale shows relative timing of development.

View larger version (25K): [in a new window]   Fig. 2. A model of cell-cell adhesion during aggregation. (A) During early aggregation, cells express DdCAD-1 (red), which is enriched on F-actin-containing filopodia. (F-actin is shown in green.) Cells initially contact make through these filopodia. (B) As cells form and enter the streams, csA (blue) is expressed at the points of contact. DdCAD-1 is relocated to cell surfaces facing away from the streams.

View larger version (13K): [in a new window]   Fig. 3. Morphogenesis in the mound. (A) Within the mound, cell movement switches from directly towards the aggregation centre to rotation perpendicular to the tip axis. In addition, differentiation into the precursor cells of the fruiting body begins. The pstA and pstO cells move into the tip, and pstB cells move to the base. Pre-spore cells occupy the central region of the mound. (B) LagC/gp150 is required for cell-cell adhesion and, through the transcription factor GBF, for the switch in the direction of movement and cell differentiation. G-box-binding factor (GBF) is required for lagC/gp150 expression, which creates a feedback loop. (C) Cell differentiation requires GskA activity. This is regulated by extracellular cAMP through two receptors, cAR3 and cAR4. At low cAMP, cAR3 activates GskA activity through ZAK1; at high concentrations cAR4 inhibits GskA activity. GskA regulates the pstB–pre-spore ratio.

View larger version (35K): [in a new window]   Fig. 4. Formation of the fruiting body. (A) The slug contains a pre-pattern that presages culmination. The pstAB cells form an inverted cone structure within the slug tip. These cells mark the future entrance to the stalk tube and are the first cells to enter the stalk. As culmination proceeds, they embed into the basal disc. When development passes directly from mound to culmination, the basal disc is formed from the pstB population. During slug migration, pstB cells are lost and re-differentiate from the anterior-like cells (ALC). The ALC are also a source of the pstO cells. During culmination, pstO cells differentiate into pstA cells and then into stalk cells within the stalk tube. The upper and lower cup structures form from pstO and pstB populations, respectively. (B) During culmination, the stalk tube forms a constriction just below its entrance. A transverse section of this region shows that the cells surrounding this stalk tube are connected by electron-dense adherens junctions (AJ) and actin filaments (AF). Reprinted by permission from Nature 408:727-731 copyright 2000 Macmillan Magazines Ltd.

View larger version (13K): [in a new window]   Fig. 5. Comparison of GSK-3/ß-catenin signalling in Dictyostelium and animals. (A) Extracellular cAMP activates GskA through cAR3/ZAK1 and inhibits it through cAR4. GskA positively regulates the ß-catenin homologue, Aar. (B) The extracellular ligand Wnt-1 stimulates the co-receptors Frizzled (Fz) and LRP5 (or LRP6) to inhibit GSK-3 function through Dishevelled (Dsh). GSK-3 negatively regulates ß-catenin. (C) In nematodes, the Wnt homologue, MOM-2, acts positively on GSK-3 function via the Fz protein MOM-5. GSK-3 appears to positively regulate the ß-catenin homologue WRM-1.