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1791 A Turning Point The Nature Of

1791 A Turning Point The Nature Of

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Download PDF Engrailed 2 En2a homeodomain transcription factor, is expressed in a caudal-to-rostral gradient in the developing tectum. This is thought to be crucial for setting up the gradients of axon guidance cues that are important for topographic map formation in the vertebrate visual system. However, the results of a new study show that En2 can also affect axon turning by interacting with the translational machinery in the growth cone. En2 contains a few protein domains involved in nuclear export, secretion and internalization, and can be secreted and transferred from one cell to another.

1791 A Turning Point The Nature Of

These features are unorthodox for a transcription factor and have long intrigued researchers. Brunet and colleagues set out to solve this mystery and tested the effect of an En2 gradient on axon turning in vitro. Interestingly, Xenopus nasal axons were attracted by En2, whereas temporal axons were repelled. These opposite turning responses correspond to the in vivo organization of the retinotectal map, in which nasal axons terminate in the En2-rich caudal tectum but temporal axons avoid it.

1791 A Turning Point The Nature Of

En2 was rapidly internalized by living growth cones. This process seems to be crucial for the effect of En2 on axon turning, as a mutant form of En2 that was defective in internalization also had no effect on growth cones. Next, the researchers studied whether the turning responses required involvement of the cell body and whether gene expression and protein synthesis were necessary. Nasal growth cones transected from their cell bodies still turned towards an En2 gradient, and isolated temporal growth cones continued to turn away from this gradient.

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These responses were blocked by protein synthesis inhibitors, but not transcription inhibitors, which indicates that nascent protein synthesis in the growth cone is necessary for its turning responses to En2. But how does En2 regulate the translational machinery in the growth cone? Like many other homeodomain proteins, En2 contains a highly conserved binding site to enkaryotic initiation factor 4E eIF4E that is typically found in translational machinery. En2 can bind to link, and Brunet et al. It is thought that 4E-BP1 silences translation by competitively binding to eIF4E and sequestering it from the translation initiation complex.

1791 A Turning Point The Nature Of

This elegant study has unravelled a new mechanism whereby the concentration gradient of En2 is used to guide axon growth. Whether other transcription factors have a similar role remains to be seen.]

1791 A Turning Point The Nature Of

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She directs the genomics platform at the Broad Institute in Cambridge, Massachusetts. For how many papers were you lead author? None — which speaks to the highly collaborative nature of the work we do here. Was it difficult to publish this many highly cited papers? Credit: Maria Nemchuk With so many good ideas springing up for projects, the challenge is keeping up with what technical advances need to come next. One of the Broad's founding principles is to make possible the types of project that are not feasible in individual research labs. We built sequencing and microarray capabilities that enable very large projects. For example, most of the papers I am working on right now are about identifying new regions of genes that may be implicated in a specific disease. The research bottleneck happens at the next step, which is the follow-on research that investigates which genome variations result in cancer. Do you have a recent favourite?

2022-04-21

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