Question

1. (8 points) Digit patterning. Alan Turing proposed the following mechanism: two diffusing morphogens that activate or inhibit each other, could result in a wave pattern that could be used to set up a developmental pattern. Raspopovic et al. demonstrate a Turing network is involved in setting up digit patterning in the limb bud. Three gene products are involved. Sox9 is a transcription factor and is expressed in cells that become digits. The ligands BMP2 (bone morphogenetic protein) and WNT are the morphogens that interact with Sox9 cells. BMP2 and WNT are expressed in the interdigital space. BMP activates Sox9+ cells and promotes digit fates in those cells. WNT inhibits Sox9 in the interdigit space. See figure for more detail on the interactions that result in an alternating expression pattern. Early Limb bud axis specification Anterior Posterior Limb bud outgrowth Late Periodic digit pattern d1 d2 d3 d4 d5 Three node BSW Turing Model Wnt Bmp Sox9 d2 d3 d4 Wnt Bmp Sox9 How to make a hand. The antero-posterior limb bud axis is specified early in development by posterior SHH signaling (upper left scheme, graded SHH signaling indicated in orange-brown). A three-node Turing network composed of the WNT and BMP signaling pathways and the Sox9 transcriptional regulator expressed by digit progenitors interact to determine the periodic digit pattern (lower schemes). WNT signal transduction (blue) inhibits Sox9 in the prospective interdigit, while the periodic Bmp2 expression (green) in the interdigit tissue stimulates Sox9 expression in the mesenchymal cells that form the digit primordia (red, upper right scheme). The periodic Sox9-positive domains that give rise to digits are indicated as d1 to d5 with anterior to posterior sequence (thumb to little finger). Below, draw in where Sox9 is expressed in the limb bud in (a) wnt null mutant, (b) Bmp2 null mutant, and transgenic animal (c) overexpressing Bmp2 (d) overexpressing Wnt. Include a sentence for each explaining why the Sox9 expression looks like what you've drawn (or how it differs from wildtype (wt)). wt Bmp2- Wnt- overex Bmp2 overex Wnt

1. (8 points) Digit patterning. Alan Turing proposed the following mechanism: two diffusing morphogens that activate or inhibit each other, could result in a wave pattern that could be used to set up a developmental pattern. Raspopovic et al. demonstrate a Turing network is involved in setting up digit patterning in the limb bud. Three gene products are involved. Sox9 is a transcription factor and is expressed in cells that become digits. The ligands BMP2 (bone morphogenetic protein) and WNT are the morphogens that interact with Sox9 cells. BMP2 and WNT are expressed in the interdigital space. BMP activates Sox9+ cells and promotes digit fates in those cells. WNT inhibits Sox9 in the interdigit space. See figure for more detail on the interactions that result in an alternating expression pattern.

Early Limb bud axis specification
Anterior
Posterior
Limb bud outgrowth

Late Periodic digit pattern
d1 d2 d3 d4 d5

Three node BSW Turing Model
Wnt Bmp Sox9

d2 d3 d4
Wnt Bmp Sox9

How to make a hand. The antero-posterior limb bud axis is specified early in development by posterior SHH signaling (upper left scheme, graded SHH signaling indicated in orange-brown). A three-node Turing network composed of the WNT and BMP signaling pathways and the Sox9 transcriptional regulator expressed by digit progenitors interact to determine the periodic digit pattern (lower schemes). WNT signal transduction (blue) inhibits Sox9 in the prospective interdigit, while the periodic Bmp2 expression (green) in the interdigit tissue stimulates Sox9 expression in the mesenchymal cells that form the digit primordia (red, upper right scheme). The periodic Sox9-positive domains that give rise to digits are indicated as d1 to d5 with anterior to posterior sequence (thumb to little finger).

Below, draw in where Sox9 is expressed in the limb bud in (a) wnt null mutant, (b) Bmp2 null mutant, and transgenic animal (c) overexpressing Bmp2 (d) overexpressing Wnt. Include a sentence for each explaining why the Sox9 expression looks like what you've drawn (or how it differs from wildtype (wt)).

wt
Bmp2-
Wnt-
overex Bmp2
overex Wnt

1. (8 points) Digit patterning. Alan Turing proposed the following mechanism: two diffusing morphogens that activate or inhibit each other, could result in a wave pattern that could be used to set up a developmental pattern. Raspopovic et al. demonstrate a Turing network is involved in setting up digit patterning in the limb bud. Three gene products are involved. Sox9 is a transcription factor and is expressed in cells that become digits. The ligands BMP2 (bone morphogenetic protein) and WNT are the morphogens that interact with Sox9 cells. BMP2 and WNT are expressed in the interdigital space. BMP activates Sox9+ cells and promotes digit fates in those cells. WNT inhibits Sox9 in the interdigit space. See figure for more detail on the interactions that result in an alternating expression pattern.

Early Limb bud axis specification
Anterior
Posterior
Limb bud outgrowth

Late Periodic digit pattern
d1 d2 d3 d4 d5

Three node BSW Turing Model
Wnt Bmp Sox9

d2 d3 d4
Wnt Bmp Sox9

How to make a hand. The antero-posterior limb bud axis is specified early in development by posterior SHH signaling (upper left scheme, graded SHH signaling indicated in orange-brown). A three-node Turing network composed of the WNT and BMP signaling pathways and the Sox9 transcriptional regulator expressed by digit progenitors interact to determine the periodic digit pattern (lower schemes). WNT signal transduction (blue) inhibits Sox9 in the prospective interdigit, while the periodic Bmp2 expression (green) in the interdigit tissue stimulates Sox9 expression in the mesenchymal cells that form the digit primordia (red, upper right scheme). The periodic Sox9-positive domains that give rise to digits are indicated as d1 to d5 with anterior to posterior sequence (thumb to little finger).

Below, draw in where Sox9 is expressed in the limb bud in (a) wnt null mutant, (b) Bmp2 null mutant, and transgenic animal (c) overexpressing Bmp2 (d) overexpressing Wnt. Include a sentence for each explaining why the Sox9 expression looks like what you've drawn (or how it differs from wildtype (wt)).

wt
Bmp2-
Wnt-
overex Bmp2
overex Wnt

Added by Hunter E.

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