• Home
  • Textbooks
  • Physical Biology of the Cell
  • Biological Patterns: Order in Space and Time

Physical Biology of the Cell

Rob Phillips, Jane Kondev, Julie Theriot

Chapter 20

Biological Patterns: Order in Space and Time - all with Video Answers

Educators


Chapter Questions

02:23

Problem 1

The French flag model shown diagrammatically in Figure 20.3 states that the spatial location of developmental decisions, such as the expression of a gene, are made by reading out different levels of a morphogen gradient. As a result, if we were to change the shape of the input morphogen, there should be a corresponding change in the downstream transcriptional decisions.
(a) Model the Bicoid gradient in Drosophila melanogaster as an exponential with decay constant $\lambda$ and concentration at $x=0$ of $[\mathrm{Bcd}]_{0} .$ Under these conditions, a certain gene is expressed at position $x_{0}$. What concentration of Bicoid is there at the point $x_{0} ?$ How would the position of the expression of the gene change if we were to change the overall Bicoid concentration by a factor a?
(b) Let's assume that a feature in Drosophila development such as the cephalic furrow, the boundary between the body of the fly and the structure that will give rise to its head, is determined solely by the Bicoid gradient. Given that for the wild-type case the furrow occurs at about $35 \%$ egg length. how would you expect the furrow to move if the dosage of the bicold gene were changed by adding or subtracting copies of gene on the genome? This question was asked by Driever and Nússlein-Volhard (1988) by creating mutant flies with different dosages of Bicoid, as shown in Figure 20.37 Compare their data for the displacement of the cephalic
furrow with the model calculated in (a) by plotting them together. Does the model hold? Discuss the possible explanations. (Relevant data for this problem can be found on the book's website.

Sana Riaz
Sana Riaz
Numerade Educator
04:07

Problem 2

(a) The average length of a gene in Drosophila melanogaster is about 11 kb and the average elongation rate of a transcript is about $1.2 \mathrm{kb} / \mathrm{min}$. How does the time to produce an average mRNA compare with the nuclear cycle times in the initial stages of fly development? For example, nuclear cycles 9 through 11 last no more than 6 minutes. while nuclear cycle 12 lasts about 10 minutes and cycle 13 lasts approximately of 12 minutes. How do the genes that are actually expressed in this stage compare with the average gene in terms of their lengths? You can search for the size of these genes by going to http://flybase.org and searching for hb (hunchback), gt (giant), kr (krüppel), and kni (knirps).
(b) When Drosophila eggs are laid, they already contain mRNA for several "maternal factors." Bicoid is an example of such a factor. Its mRNA is localized at the anterior end of the embryo, serving as a source of Bicoid protein. It is essentially stable up until the end of nuclear cycle $14,$ when it gets actively degraded. In this problem, we want to estimate the number of mRNA molecules deposited in the embryo by its mother. To make this estimate, we appeal to measurements of the number of Bicoid proteins at nuclear cycle $14 .$ Assume that all Bicoid is localized to the nuclei. which at cycle $14,$ approximately 120 minutes after the egg has been laid, have a radius of about $3.3 \mu \mathrm{m}$. Use the data shown in Figure $20.6(\mathrm{B})$ in order to estimate the total number of Bicoid molecules in the whole embryo at this point. Assuming that translation of bicoid mRNA is constant, estimate the number of mRNA molecules that led to your calculated number of Bicoid proteins. You might find it useful to estimate the number of ribosomes per kb on a transcript from Figure $3.13(\mathrm{p} .108)$ and to use the translation rate discussed in Section $3.2 .1(\mathrm{p} .107)$

Sana Riaz
Sana Riaz
Numerade Educator
02:15

Problem 3

In Equation $20.33,$ we wrote the equations describing the dynamics of Turing's simplest reaction model. Construct a phase portrait that shows the dynamics of the system.

Sana Riaz
Sana Riaz
Numerade Educator
03:14

Problem 4

In the chapter, we considered a one-dimensional lattice of cells, each containing two species of morphogens that undergo chemical reactions. Following Turing, we showed that diffusion of morphogens can destabilize a steady state described by a uniform concentration profile, leading to a spatially periodic pattern of morphogens. In this problem, we analyze the situation when there is only one morphogen species present.
(a) Rewrite the reaction-diffusion equation for the Turing system, Equation $20.40,$ for the case of a single morphogen whose concentration within a cell is $Y_{r}$. Then consider a small periodic perturbation of the uniform steady state $Y_{r}=Y^{*}$ of the form $Y_{r}=Y^{*}+y(t) e^{i(2 \pi r / \lambda)}$ and derive the dynamical equations for the amplitude $y(t)$
(b) Assuming that there are $N$ cells in the system and that they are arranged in a ring so that the $r=1$ cell has the $r=N$ and $r=2$ cells as its nearest neighbors, what are the allowed values of the wavelength $\lambda$ for the periodic perturbation?
(c) Derive the conditions under which the uniform steady state is unstable to a small periodic perturbation. Argue that this one-component Turing system does not lead to spatially periodic pattern of morphogen concentration.

Sana Riaz
Sana Riaz
Numerade Educator
02:14

Problem 5

Replace the discrete treatment of the Turing instability in a one-dimensional system discussed in the chapter with the corresponding continuum reaction-diffusion equations
$$\begin{array}{l}
\frac{\partial X}{\partial t}=D_{x} \frac{\partial^{2} X}{\partial x^{2}}+f(X, Y) \\
\frac{\partial Y}{\partial t}=D_{y} \frac{\partial^{2} Y}{\partial x^{2}}+g(X, Y)
\end{array}$$
for the morphogen concentrations $X$ and $Y$, which are both functions of position. Like for the case analyzed in the chapter, the functions $f(X, Y)$ and $g(\bar{X}, Y)$ reflect the chemical interactions between the morphogens. Also. we introduce the notation
$$\begin{array}{l}
a_{11}=\left.\frac{\partial f}{\partial X}\right|_{(h, k)}, \quad a_{12}=\left.\frac{\partial f}{\partial Y}\right|_{(h, k)} \\
a_{21}=\left.\frac{\partial g}{\partial X}\right|_{(h, k)}, \quad a_{22}=\left.\frac{\partial g}{\partial Y}\right|_{(h, k)}
\end{array}$$
where $h$ and $k$ are steady-state values of $X$ and $Y$. We are interested in the stability of the homogeneous steady state $(X, Y)=(h, k)$ with respect to a perturbation that is periodic in space, as an instability signals the spontaneous appearance of a spatially periodic pattern of morphogens.
(a) Linearize the reaction-diffusion equations in the vicinity of the fixed point $(X, Y)=(h, k) .$ Consider the time evolution of a periodic perturbation of the form $(8 X, 8 Y)=\left(\eta(t) e^{i q x}\right.$$\varepsilon(t) \mathrm{e}^{\mathrm{i} q x}$, in the vicinity of the fixed point $(h, k),$ following the same strategy that we used in the chapter. In particular, derive expressions for the eigenvalues of the rate matrix $\mathbf{A}$ analogous to the one defined in Equation $20.45,$ in terms of its determinant (DetA) and trace (Tr A).
(b) Show that a necessary condition for linear stability of
a fixed point in the absence of diffusion is that at least one of $a_{11}$ and $a_{22}$ is negative.
(c) Show that for a fixed point that is linearly stable in the absence of diffusion, a necessary condition for linear instability in the presence of diffusion is that exactly one of $a_{11}$ and $a_{22}$ is negative.
(d) Assuming that $a_{22}$ is negative, show that at a Turing bifurcation (that is, at the onset of instability: if we were to continuously adjust parameters such as reaction rate constants or diffusion constants until the fixed point just becomes unstable), the characteristic length of the emerging pattern from the homogeneous steady state (fixed point) scales like
$$\lambda^{-2} \sim \lambda_{x}^{-2}-\lambda_{y}^{-2}$$
where $\lambda_{X} \equiv \sqrt{D_{X} / a_{11}}$ and $\lambda_{y} \equiv \sqrt{D_{y} /\left(-a_{22}\right)}$
(e) Comment on the physical implications of these results. What is the wavelength of an oscillatory instability? (Problem courtesy of Justin Bois.)

Sana Riaz
Sana Riaz
Numerade Educator
02:54

Problem 6

In the chapter, we considered the dynamics of Notch and Delta in a two-cell system by taking the limit in which the decay rate of Delta is much greater than that of Notch. Here we examine the same problem in the opposite limit.
(a) Argue that in the limit $v=\gamma_{\mathrm{D}} / y_{\mathrm{N}} \ll 1,$ the Notch activity in the two cells quickly settles into a steady state. What are the resulting dynamical equations for the evolution of Delta that follow from Equations 20.54 and 20.55 in this limit?
(b) Using the functional forms for the Notch and Delta activation rates, $F\left(D^{\prime}\right)$ and $G(N),$ described in Figure 20.29 obtain a phase portrait for the dynamics of Delta in the two cells, analogous to the one shown in Figure 20.31 Based on your phase portrait, show that in the long-time limit, the system will settle into a steady state in which one cell assumes the primary fate while the other assumes the secondary fate.

Sana Riaz
Sana Riaz
Numerade Educator