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MICROBIOLOGY: ON BREAKING SYMMETRY IN MYXOBACTERIA

The following points are made by O.A. Igoshin et al (Current Biology 2004 14:R459):

1) Multicellular animals and plants develop from genetically equivalent cells, yet neighboring cells often adopt different fates. Some well-studied examples are the formation of sensory bristles from a sheet of uniform neuro-ectodermal cells in Drosophila, and the formation of hair or feathers in the uniform skin ectoderm of vertebrates. This breaking of symmetry within groups of equivalent cells depends on cell-cell interactions that stabilize themselves. Common regulatory systems that break symmetry in flies, worms, and vertebrates use cell-surface signals such as Notch, Hedgehog and Wnt.

2) Although the mechanisms of cell-cell interaction during eukaryotic organogenesis have received the most attention, genetic programs capable of breaking symmetry are also found in bacteria. The view that bacteria are asocial cells with no need for intercellular communication was demolished by the discovery of homoserine lactones which carry extracellular signals and by the phenomenon of "quorum sensing".

3) Myxobacteria are common inhabitants of the soil where they enjoy a rich social life. In behavior and development, they resemble the cellular slime molds and, in some aspects of development, animals and plants as well. Myxobacteria prey on other bacteria: feeding cooperatively, they secrete enzymes that digest their prey. They compete with other soil micro-predators and, when their prey are exhausted, they stop hunting, build multicellular fruiting bodies and sporulate for survival. This developmental program uses two cell-cell signals: first, the diffusible, quorum sensing A-signal that initiates fruiting body construction; and second, the cell surface bound C-signal that coordinates the motion of individual cells by cell-contact.

4) Myxobacteria are 5-7 microns long and about 0.5 microns in diameter, and they can bend. Unable to swim, they glide in the direction of their long axis on a surface using two different motors: a pulling motor at the leading pole of the cell, and a pushing motor at the trailing pole. Fibrils serve as anchors for their pulling motors: retracting type IV pili are evident as a web of thin strands that connect adjacent cells. Even though the cells are flexible, they rarely make U-turns; instead, they simply reverse their direction by trading head motors for tail motors. Contact-mediated C-signals regulate movement by altering the probability of a cell reversing direction.

5) Even isolated cells do not reverse at random, for their reversal times do not follow a Poisson distribution. Preceding the construction of a fruiting body a culture frequently -- but not always -- passes through a phase when all of the bacteria undergo fairly synchronized periodic reversals. The synchronization manifests itself in the formation of the traveling density waves: heaps of cells travel as wave crests, with cells in each heap oriented along their long axes in the direction of wave propagation. The high cell density crests are separated from each other by troughs of lower cell density.

6) Remarkably, counter-propagating wave crests appear to pass through one another, because the unique shape of an advancing wave front is preserved after the collision. But the colliding waves only appear to interpenetrate: actually they reflect from each other. Reflection takes place at the level of individual cells that exchange C-signal when they collide end-to-end, and then respond to the signal by reversing their gliding direction. This type of wave differs from the developmental waves of the cellular slime mold Dictyostelium discoideum that are generated by diffusible morphogens and annihilate upon collision.(1-4)

References:

1. Igoshin, O.A., Welch, R., Kaiser, D., and Oster, G. (2004). Waves and aggregation patterns in Myxobacteria. Proc. Natl. Acad. Sci. USA 101, 4256-4261

2. Igoshin, O.A., Mogilner, A., Welch, R.D., Kaiser, D., and Oster, G. (2001). Pattern formation and traveling waves in myxobacteria: Theory and modeling. Proc. Natl. Acad. Sci. USA 98, 14913-14918

3. Kaiser, D. (2003). Coupling cell movement multicellular development in myxobacteria. Nat. Rev. Microbiol. 1, 46-54

4. Lewis, J. (2003). Autoinhibition with transcriptional delay: A simple mechanism for the zebrafish somitogenesis oscillator. Curr. Biol. 13, 1398-1408

Current Biology http://www.current-biology.com

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Related Material:

ON PATTERN FORMATION BY A BACTERIAL POPULATION

The following points are made by L. Jelsbak and L. Segaard-Andersen (Proc. Nat. Acad. Sci. 2002 99:2032):

1) Formation of spatial patterns of cells from a mass of initially identical cells is a recurring theme in developmental biology. The dynamics that direct pattern formation in biological systems often involve morphogenetic cell movements (1-3). An example is fruiting body formation in the gliding soil bacterium Myxococcus xanthus in which an unstructured population of identical cells rearranges into an asymmetric, stable pattern of multicellular fruiting bodies in response to starvation (4).

2) M. xanthus cells are rod shaped and move by gliding, a process whereby a bacterial cell moves in the direction of its long axis on a solid surface (5). Fruiting body morphogenesis absolutely depends on starvation of cells at a high cell density on a solid surface (4). It represents a true de novo pattern formation process as it starts from a homogeneous and symmetric population of starving cells, and occurs without the contribution of external cues. In the presence of nutrients, M. xanthus cells form cooperatively spreading swarms. In response to starvation, swarming behavior is constrained, and, after 6 hours of starvation, small aggregates are evident. Some of these aggregates enlarge into hemispheres as a consequence of continued accumulation of cells, and, after 24 hours, haystack-shaped fruiting bodies have formed, each containing 100,000 densely packed cells. Within the nascent fruiting bodies, the motile, rod-shaped cells differentiate into non-motile spores. Aggregates that do not mature into fruiting bodies dissipate as their cells migrate to other aggregation centers. Before the appearance of aggregation centers, cells become organized in streams, in which the cells are arranged end-to-end and with their long axes roughly in parallel with each other, and cells move toward the aggregation centers organized in these streams.

3) Aggregation is induced by the cell surface-associated "C-signal", the latest acting of several extracellular signals required for fruiting body morphogenesis. The C-signal is a cell surface-associated protein encoded by the csgA gene. Cells that carry mutations in the csgA gene are conditionally defective in aggregation and sporulation. The developmental defects in csgA cells are rescued by codevelopment with wild-type cells. This "extracellular complementation" is based on wild type cells providing the missing C-signal to the csgA cells, thus enabling them to complete their development. The level of C-signaling increases during development because of accumulation of the C-signal. The C-signal induces aggregation and sporulation in a concentration-dependent manner, i.e., intermediate level aggregation is induced and at high levels sporulation is induced. C-signal transmission occurs by a contact-dependent mechanism that involves end-to-end contacts between cells and fails when cells are unable to make these even though they are able to make side-by-side contacts.

References (abridged):

1. Le Douarin, N. M. (1984) Cell 38, 353-360

2. De Felici, M. , Dolci, S. & Pesce, M. (1992) Int. J. Dev. Biol. 36, 205-213

3. Melchers, F. , Rolink, A. G. & Schaniel, C. (1999) Cell 99, 351-354

4. Dworkin, M. (1996) Microbiol. Rev. 60, 70-102

5. Spormann, A. M. (1999) Microbiol. Mol. Biol. Rev. 63, 621-641

Proc. Nat. Acad. Sci. http://www.pnas.org

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Related Material:

A NEW METHOD FOR FOLLOWING INDIVIDUAL CELLS IN SLIME MOLD

Notes by ScienceWeek:

Dictyostelium discoideum is an organism that has been intriguing biologists for most of this century. Although this organism is often called a "cellular slime mold", it is not a mold and it is not consistently slimy. A better common name for it is a "social amoeba". What is most remarkable about the organism is its life cycle. In one part of it life cycle, the "organism" consists of individual dispersed amoebas living on decaying logs, eating bacteria and reproducing by binary fission like most other protozoans. Then, when the local food supply becomes exhausted, a rather astounding event occurs: tens of thousands of these amoeba join together to form moving streams of cells that converge at a central point, and there they aggregate to produce a slug (grex) 2 to 4 millimeters long.

The slug migrates as a single body towards light, and when it reaches an illuminated area, migration ceases, and the slug differentiates into a fruiting body composed of spore cells and a stalk, the stalk rising approximately 1 centimeter high above the plane of the surface on which the slug has migrated. Inside the globular end of the fruiting body, each spore cell is cellulose encapsulated. In the denouement, the stalk cells die and the spore cells are widely dispersed to become new amoeba, each of which will begin a separate new population of cells both individual and social.

Thus, in this organism, initially identical cells are differentiated into one of two alternative cell types, spore cells and stalk cells. It is an organism where individual cells come together to form a cohesive structure, aggregating into a single organism, a quite remarkable feat of organization that challenges biologists, chemists, and physicists. Much has been learned about this organism in the past few decades, in particular the apparent important role of release of cyclic adenosine monophosphate (cAMP) in the initial aggregation that produces the slug.

The following points are made by J.T. Bonner (Proc. Nat. Acad. Sci. 1998 95:9355):

1) The author (who has spent more than 50 years studying the social amoeba) points out that one of the obstacles in studying D. discoideum is that it has been difficult to follow the movements of individual cells within the slug. The author now describes a new method for studying D. discoideum, the method producing flat slugs one cell thick at a mineral oil-water interface where one can follow the movement of all the cells.

2) The author reports that observations of time-lapse videos reveal the following about slug migration:

a) While the posterior cells move straight forward, the anterior cells swirl about rapidly in a chaotic fashion.

b) Turning of the slug involves shifting the high point of these hyperactive cells.

c) Both the anterior and posterior cells move forward on their own power as the slug moves forward.

d) There are no visible regular oscillations within the slug.

e) The number of prestalk and prespore cells is proportionate for a range of sizes of the mini-slugs involved in these experiments (approximately 300 to 400 cells in each of these mini-slugs).

3) The author suggests that all of the observations on thin slugs are consistent with observations of normal 3-dimensional slugs, and that experiments with 2-dimensional slugs may provide new insights into differentiation and movements in this organism.

Proc. Nat. Acad. Sci. http://www.pnas.org

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