Journal club

Below is the PowerPoint I presented in the journal club this morning. It's a summary of a recent paper about laterality in the nematode worm:

  • Poole, R. J. & Hobert, O. (2006). Early embryonic programming of neuronal left/right asymmetry in C. elegans. Curr. Biol. 16: 2279-2292. [PDF]

I mentioned this study in yesterday's post about asymmetry in the nervous system, without going into too much detail. I'm sharing the presentation here because, although the paper is quite complex, the experiments described in it are very elegant.  

When it comes to using PowerPoint, I'm a minimalist. I put as little text as possible on each slide, so as not to overwhelm the audience. I also don't like using much animation in the slides. The presentation is as much for my benefit as it is for the audience's: each slide is a visual cue that reminds me about the points I need to make during the talk.

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Slide 1: The left and right taste neurons (ASEL and ASER, respectively) are mirror images of each other; i.e. their axodendritic morphologies and synaptic connections are perfectly symmetrical.

However, expression of the gcy family of G-protein coupled taste receptors in the cells is asymmetrical. ASEL expresses some receptors form the family, and ASER expresses others. (gcy-7 is a molecular marker for ASEL, and gcy-5 is a marker for ASER.)

These asymmetrical gene expression patterns produce a functional asymmetry - ASEL detects sodium ions, while ASER detects chloride ions.

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Slide 2: At the 8-cell stage, the embryo consists of 8 identical blastomere cells. ASEL and ASER arise from asymmetrical cell lineages that are generated on opposite sides of the embryo. ASEL is generated from blastomere ABalp (in red), and ASER is generated from ABpra (in blue). At the 2- and4-cell stage, a Notch-Delta signalling event is involved in specifiying the left/right identities of the blastomeres.

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Slide 3: At the 64-cell stage, the ASE neurons are in an equipotent hybrid state, in which they both express all members of the gcy receptor family. In other words, they are not fully differentiated. 

The cells then acquire their asymmetrical fates following a signalling event that establishes the asymmetrical expression of gcy genes in the cells. In one of the cells, microRNAs bind to, and prevent translation of, gcy-5 transcripts, so that the cell acquires ASER identity.

The authors tested two models of how left-right asymmetry of the ASE cells is established. According to one model, the signalling mechanism at the 64-cell stage is what determines the fate of the cells. The other holds that left/right identity is established in the blastomeres at the 8-cell stage. 

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Slide 4: Ablation of ABalp results in the failure to generate ASEL, as well as all the other cells derived from that blastomere. ASER is present even in the absence of the ASEL, and vice versa, suggesting that the late signalling event is not what specifies left/right identity in these cells.

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Slide 5: At the 6-cell stage, a rotation of the mitotic spindle breaks the symmetry of the embryo, giving cells on each side of the embryo a left/right identity. (The spindle is a scaffold along which chromosomes align when they replicate and segregate prior to cell division.) In gpa-16 mutants, this spindle rotation is randomized. As a result, laterality in some worms is reversed.

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Slide 6: The unmutated gpa-16 gene is heat-sensitive. The gene's activity can therefore be abolished at any stage of development if the temperature at which the worms are kept is altered.

Abolishing gpa-16 activity after the 8-cell stage did not affect laterality, showing that the reversal of laterality in gpa-16 mutants is not due to some other activity that is independent of the spindle rotation.

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Slide 7: Notch-Delta signalling at the 8-cell stage activates T-box transcription factors in the blastomeres on one side of the embryo, and inhibits the same genes in the blastomeres on the other. This provides the blastomeres with information about laterality.

The Notch receptor gene glp-1 is heat-sensitive, so Notch-Delta can be abolished at any time (as in the previous slide). Disrupting this signal at the 8-cell stage causes ectopic cell lineages (i.e. the lineage derived from the ABalp blastomere is found on the right, or the lineage derived from ABpra is on the left). In these ectopic lineages, the ASE cells retain their original identity.

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Slide 8: If a late signalling signal is involved in establishing laterality in ASE cells, then the signal must originate in adjacent cells (either the other in the pair, or interneurons).

If all but the ABalp blastomere are ablated with a laser, the majority of cells that would normally be adjacent to ASEL are missing.   

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Slide 9: tbx-37 and tbx-38 are the genes encoding the T-box transcription factors that are activated/ inhibited by Notch-delta signalling at the 8-cell stage.


Slide 10: How the left/right identity of the blastomeres is established remains unknown. It could be an epigenetic mechanism that primes cells for a specific identity. The chromatin modifications would be inherited by cells generated later on within that lineage.

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