BIO 202 — Lesson 25

A

A limb bud on the side of an embryo, the body to the left. Cells along its tip make Fgf8, and while they do, the bud grows. It runs as you watch.
Its parts go in one at a time: Fgf8 at the tip; Bmp4, which shuts the tip's Fgf8 off; Grem1, which blocks Bmp4; Grem1 made only where Shh reaches.
Yours to set: how fast Fgf8, Shh and Grem1 are transcribed.

A limb bud seen from above, the body to the left, growing to the right. The ruler counts rows of cells from the body; its heavy stretch is the bud now. The hour in the corner is the time since the bud began.Blue along the tip: the cells there making Fgf8. A dashed tip: they have stopped.Orange: Shh, made by the patch of cells at the bud's back edge near the body and spreading from it; the dashed orange line is as far as it reaches. Hatching: Grem1, darker where there is more. Red dots: Bmp4 that Grem1 has not blocked.▾ marks where the tip was every 5 hours. The bar at the top right is Bmp4 at the tip; past the mark, the tip's Fgf8 shuts off.

fast pause

PartsThe bud starts with its first part alone. Add the next part puts in the next one; a tick box switches a part off and on again.Adding or switching a part starts the bud again.

The cells along the tip transcribe Fgf8; while they do, the bud grows.

Fgf8

Fgf8 transcriptionFgf8 is transcribed in the cells along the bud's tip. Its protein keeps the cells under the tip dividing, so the bud grows while the tip makes it: 1.8 rows of cells an hour at ×1.

Shh

Shh transcriptionShh is transcribed in a patch of cells at the back edge of the bud, near the body. Its protein spreads out from there; with more of it, it reaches farther, and the bud's end is wider.Held until Shh is in the model.

Grem1

Grem1 transcriptionGrem1 protein binds Bmp4 and blocks it. Bmp4 at the tip that is not blocked shuts the tip's Fgf8 off.Held until Grem1 is in the model.

To finish

A bud that grows, then stops itself
One that stops longer than with every gene at ×1
One that stops shorter than with every gene at ×1
The length it has at ×1, reached sooner

R code

B

Stage A's bud with every part in. As the tip grows away, the cells it leaves behind switch Sox9 on in stripes, row by row, and where Sox9 is on, cartilage forms.
The parts go in one at a time: Sox9 in the cells the tip leaves behind; joints, one for every 4.2 hours the tip keeps growing; Bmp4 made between the digits, where it makes cells die.
Yours to set: how fast Fgf8, Shh and Grem1 are transcribed, and Bmp4 between the digits.

The limb seen from above, the body to the left, a column of cells for each row the tip has left behind. Black: cells with Sox9 on, which make cartilage.Blue along the tip: the cells there still making Fgf8.A joint is a gap across a digit. Dashed outlines: tissue and digits lost to cell death.Under the limb, each part counted. The ruler counts rows of cells from the body; its heavy stretch is the limb now.

fast pause

PartsAdd the next part puts in the next one; a tick box switches a part off and on again.Adding or switching a part grows the limb again.

The bud of stage A grows and stops itself.

Fgf8

Fgf8 transcriptionFgf8 is transcribed along the tip; the bud grows while the tip makes it.A change made after the limb has stopped grows it again.

Shh

Shh transcriptionShh is transcribed at the back edge of the bud, near the body; with more of it, it reaches farther, and the bud's end is wider.

Grem1

Grem1 transcriptionGrem1 is made where Shh reaches; its protein blocks Bmp4, which would shut the tip's Fgf8 off.

Bmp4

Bmp4 transcription between the digitsBmp4 transcribed in the cells between the digits makes them die once the limb has stopped. Less of it, and the cells between the digits live. More, and cells die inward from the limb's two edges, taking the digits there; the middle one or two always stay.It acts on a finished limb at once. Held until it is in the model.

To finish

Six digits or more
Three digits or fewer, none lost to cell death
Three digits or fewer, from five or more laid down
A web between the digits
Six bones or more in a digit

R code

C

Stage B's limb with every part in. It starts as a human arm.
Five limbs, each grown by this same model at some setting of the four genes. Build any four.
Yours to set: how fast Fgf8, Shh and Grem1 are transcribed, and Bmp4 between the digits.

Stage B's limb: black where Sox9 is on, blue along the tip while it makes Fgf8, gaps for joints, dashed outlines for what cell death removed.A change made after the limb has stopped grows it again; Bmp4 between the digits acts on it at once.

fast pause

Fgf8

Fgf8 transcriptionFgf8 is transcribed along the tip; the bud grows while the tip makes it.

Shh

Shh transcriptionShh is transcribed at the back edge of the bud, near the body; with more of it, it reaches farther, and the bud's end is wider.

Grem1

Grem1 transcriptionGrem1 is made where Shh reaches; its protein blocks Bmp4, which would shut the tip's Fgf8 off.

Bmp4

Bmp4 transcription between the digitsBmp4 between the digits makes the cells there die once the limb has stopped: less, and they live; more, and cell death eats in from the two edges.

To finish: any fourEach limb here was grown by this model at some setting of the four genes, drawn the same way, to the same scale.A finished limb like it fills its circle: the same digits kept and lost, the web or none, about as long, about as many bones in a digit.

a skink
a horse
a camel
a bat
an ichthyosaur

R code

D

The map: the digits stage C's limb ends with at each pair of Shh and Bmp4 levels, Fgf8 and Grem1 at ×1.
Clades of species, each species a limb on the map. Every step a species' Shh and Bmp4 change a little, and its digits are what the map gives there. Species split and are lost.
Yours to set: the cell a founding species starts from (click it), and which limbs split more often.

Across: how fast Shh is transcribed. Up: Bmp4 between the digits. Each cell: the digits a limb grown at those levels keeps (the number; darker for more), and one ✗ for each digit lost to cell death.Click a cell: its limb is drawn below, and a species with that limb founds the clades. A dot for each living species of clade 1, where it is now.

Clade 1: each line a species from the step it split off, shaded by its digits (the key at the right), its shade changing where its digits change; a dot marks each change. Dashed where it has digits lost to cell death. ×: a species lost.

fast pause

SplittingEach step a species splits with chance .05 (less as its clade nears 40 species) and is lost with chance .015; never the clade's last. Its Shh and Bmp4 move a normal step of .04 of a cell each step.A species whose limb is the kind chosen here splits six times as often. A change acts on the clades as they run.

All 16 clades from the same founder, a bar each: its living species split by their digits, shaded and numbered. ✗ over a clade: a digit has been lost to cell death in it.

To finish

Digit number changing in four lineages or more
Twelve species, and no change in digits
A digit lost to cell death, arising in the clade

R code

A

PartsThe bud starts with its first part alone. Add the next part puts in the next one; a tick box switches a part off and on again.Adding or switching a part starts the bud again.

Fgf8

Shh

Grem1

To finish

B

PartsAdd the next part puts in the next one; a tick box switches a part off and on again.Adding or switching a part grows the limb again.

Fgf8

Shh

Grem1

Bmp4

To finish

C

Fgf8

Shh

Grem1

Bmp4

To finish: any fourEach limb here was grown by this model at some setting of the four genes, drawn the same way, to the same scale.A finished limb like it fills its circle: the same digits kept and lost, the web or none, about as long, about as many bones in a digit.

D

To finish

Good job!