Great Experiments: The power of beads: FGF-4 beads can direct limb growth and patterning

The power of beads: FGF-4 beads can direct limb growth and patterning

Key experiments show factors required for limb development,
and show the plasticity of this process! [Source]

The process of limb development has been important for many different fields, from determining why animals would develop limbs evolutionarily, to which factors are involved. This is an even more complicated process in higher organisms which have to develop two symmetric limbs, each having its own three-dimensional, directional axes. By the 1990s, various studies had given rise to a model: the limb bud starts with a thickening of the body wall, this tissue forms a specialized epithelial structure (the apical ectodermal ridge), and this tissue requires a signal from the “polarizing region” for the limb to develop properly. However, although some molecular factors had been implicated as being the polarizing signal, the in vivo mechanism was still unknown.

In 1993, Lee Niswander and colleagues demonstrated that one specific growth factor, FGF-4, was both necessary and sufficient for limb development and patterning. They soaked beads in FGF-4 and placed them at various locations on developing limb buds in chick embryos. Through these technically creative experiments, Niswander et al. showed that FGF-4 beads, placed specifically at the posterior edge of the limb bud, could direct normal development and patterning of limbs even in the absence of the apical ectodermal ridge! These experiments ultimately suggest that it is not the distal-most tissue that is required for the growth and patterning of the embryo, but instead, that this tissue uses one signaling molecule FGF-4 to direct a specifically-localized tissue to orchestrate proper limb development.

Niswander L, et al. FGF-4 replaces the apical ectodermal ridge and directs outgrowth and patterning of the limb. Cell 75, 579-587 (1993)

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FOR COURSE PARTICIPANTS:

Our goal: to learn about important, beautifully designed experiments from across the biological and biomedical sciences.

In the course, you'll gain experience in reading classic papers and explaining key experiments from your own fields of interest to colleagues in other fields.

Students propose papers to discuss in the form of short written posts on this site. Papers to discuss are selected by class vote each week.

This course should strengthen your communication skills and your understanding of diverse fields of biology–and importantly, it should inspire creative thinking about your own research.

Writing your posts

Each person should contribute at least 4 posts about their favorite experiments by 1 month before the end of the semester (by the end of October). Please propose your own schedule for 4 posts in an email to Bob.

Please post about experiments that you consider to be (1) fundamental to an area of science and (2) beautifully designed. Experiments that changed or founded a field and also made you hit your head and say, "damn, why didn't I think of that?!" are great choices.

Posts should be 150 words or fewer, plus a picture or movie with an appropriate image credit included. Please do not exceed 150 words. This is an exercise in clear, concise writing.

Your post should be written for an intelligent audience who understands biology but knows little to nothing about the field you're writing about. Avoid confusing jargon. Informal wording is fine. Your post's title should capture what's interesting and fundamental about the work, for example the central question addressed by the work.

Please provide a link to the one paper you chose, bullet-pointed so that there's no confusion about which one this is. If you like, below the one bullet-pointed link you can also provide a link to a companion paper or two that can help put the main paper into context.

It's considered very bad form to cut and paste text from programs like Microsoft Word for your post, because hidden formatting comes along and can cause headaches. It makes me sad. A tip: copying your text from Word into a Google search bar, and then copying that text from the search bar, eliminates the formatting.

You can modify your posts at any time. It's okay to rewrite your dusty old posts to try to re-invigorate interest.

Voting

Voting will take place each Friday until 5pm on a poll that will be sent to you. Each poll will generally include all posts that are up by that Friday at 8am.

Please vote every week. Please don't vote for your own selections. The voting will decide which paper we'll read for the following week's meeting. Posts that are getting few or no votes will be removed periodically.

Meetings

We'll meet each Thursday at 12:30pm in GSB3101. Each week, we'll discuss the winning paper. The person who chose it will present it along with anything else that seems relevant, with everyone's help, tolerating constant interruptions for some interesting discussion.

An important part of the course: Everyone else should plan to present one other thing briefly and informally to everyone–a related paper, some historical background, or anything at all you chose to explore because you found it interesting and relevant. Come prepared to answer questions, since we're all curious.

If you don't have time to do the readings one week, please skip the meeting that week. This way, everyone who comes will be full participants. No one will be badgered for missing just 1 or 2 meetings, I swear.

-Bob Goldstein