rules of evidence IIa 001 - SIDEUGHTS SPECULATIONS Rules of...

Unformatted text preview: SIDEUGHTS SPECULATIONS Rules of Evidence ll: Controls something is and about concluding what something is not. A piece of sci— entific evidence is only as good as the con— trols it uses to tell what something is not, and the difference between science and non-science is usually a matter of controls. Just because a particular compound causes cells in the same population to differentiate into particular cell types does not mean that it is a morphogen. S cience is both about concluding what Negative controls In TheAdventure ofBlack Peter, Sherlock Holmes noted, “One should always look for a possible alternative and provide against it.” What-other possibilities could there be be- sides the morphogen hypothesis? A mor- phogen is a diffusible molecule that acts through a concentration gradient. However, there are at least two other possibilities be- sides gradients to explain the phenomenon whereby cells appear to differentiate with re- spect to their proximity-to a source of Nodal. First, there could be a cascade of induc- tions. Nodal might only induce nearby cells at high concentrations and do nothing at lower concentrations. insteadr the induced cells might put forth a second signal that induces the next set of cells, and these cells might put forth a third local signalr and so on. Such a sequence of events is sometimes called a relay cascade. A second possibility is that the cells near the source of Nodal might respond not only by differentiating, but by migrating away to a distant position within the responding tissue (or by producing daughter cells that migrate). The stronger the signal, the farther away the induced cells ortheir daughters migrate. Nodal mRNA + dye Ttansplanted cells do not respond to Nodal \ i i 1‘ 25314.“5.‘6.‘7.’8.'9.‘10 1’ 2/ 314/51657I839I10 - goosecoid {head mesoderm) Transplanted cell I floating head (notochord} FIGURE 3.21 Negative controls confirm that Nodal is a mor- phogen. (A) Transplanted cells that lack the Nodal receptor do not express the g'oosecoid, floating head, or rip-tail genes when placed nearthe Nodal—secreting cell. (B) Such unresponsive cells do not block cells farther away from expressing the appropriate floating head and no-tail genes, indicating that Nodal diffusion is the most likely means of signal transmission. (C) A labeled responsive cell trans- planted to a particular location near the Nodal—secreting cell will express the gene appropriate to the distance from the Nodal-secret- ing cell. (D) If a gene encoding some other substance (in this case, bacterial |3-galactosidase, lacZJ that is not a signaling molecule, the nearby cells will not express their Nodai-responsive genes. I rip—tail (muscles) Chen and Schiei’s experiments, described in Figure 3.20 controlied for these alternative possibilities. First. to distinguish whether the effects of Nodal are due to the diffusion of Nodal or to a relay cascade, the investigators found cells that did not respond to Nodal. There are zebrafish with mutations in a receptorfor Nodal, and bias- tomeres from these fish cannot respond to Nodal protein (Figure 3.2m). (These Nodal- deficient fish have numerous developmen— tal anomalies, and the name of this mutant, one—eyedpinhead, suggests it has some major problems in forming its face.) The mutant blastomeres can be transplanted between the source of Nodal and the responsive blastomeres (Figure 3.2-1 B}. If (Continued on next page) ...
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