Ebook An introduction to systems biology design principles of biological circuits: Part 2
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Ebook An introduction to systems biology design principles of biological circuits: Part 2
Ebook An introduction to systems biology design principles of biological circuits: Part 2
CHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2n which a single cell, an egg, becomes a multicellular organism. During development, the egg divides many times to form the cells of the embryo. All of these cells have the same genome. If they all expressed the same proteins, the adult would be a shapeless mass of identical cells. During developmen Ebook An introduction to systems biology design principles of biological circuits: Part 2t, therefore, the progeny of the egg cell must assume different fates in a spatially organized manner to become the various tissues of the organism. TEbook An introduction to systems biology design principles of biological circuits: Part 2
he difference between cells in different tissues lies in which proteins they express. In this chapter, we will consider how these spatial patterns canCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2ly proteins) called morphogens. How are morphogen gradients formed? In the simplest case, the morphogen is produced at a certain source position and diffuses into the region that is to be patterned, called the field. A concentration profile is formed, in which the concentration of the morphogen is h Ebook An introduction to systems biology design principles of biological circuits: Part 2igh near the source and decays with distance from the source. The cells in the field are initially all identical and can sense the morphogen by meansEbook An introduction to systems biology design principles of biological circuits: Part 2
of receptors on the cell surface. Morphogen binds the receptors, which in turn activate signaling pathways in the cell that lead to expression of a seCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2t the cell’s position.The prototypical model for morphogen patterning is called the French flag model (Figure 8.1) (Wolpert, 1969; Wolpert et al., 2002). The morphogen concentration M(x) decays with distance from its source at X = 0. Cells that sense an M concentration greater than a threshold value Ebook An introduction to systems biology design principles of biological circuits: Part 2 T| assume fate A. Cells that sense an M lower than Tị but higher than a second threshold, T2, assume fate B. Fate c is assumed by cells that sense loEbook An introduction to systems biology design principles of biological circuits: Part 2
w morphogen levels, M < T2. The result is a three-region pattern (Figure 8.1). Real morphogens often lead to patterns with more than three different fCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2e morphogen is degraded as it diffuses, resulting in a steady-state concentration profile that decays with distance from the source at X = 0. Cells in the field assume fate A if M concentration is greater than threshold 1. fate B if M is between thresholds 1 and 2, and fate c if M is lower than thre Ebook An introduction to systems biology design principles of biological circuits: Part 2shold 2.Figure 8.1 depicts a one-dimensional tissue, but real tissues are three-dimensional. Patterning in three dimensions is Otten broken down intoEbook An introduction to systems biology design principles of biological circuits: Part 2
one-dimensional problems in which each axis of the tissue is patterned by a specific morphogen.Complex spatial patterns are not formed all at once. RaCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2subpatterns. Some patterns require the intersection of two or more morphogen gradients. In this way, an intricate spatial arrangement of tissues is formed. The sequential regulation of genes during these patterning processes is carried out by the developmental transcription networks that we have dis Ebook An introduction to systems biology design principles of biological circuits: Part 2cussed in Chapter 6. Additional processes (which we will not discuss), including cell movement, contact, and adhesion, further shape tissues in compleEbook An introduction to systems biology design principles of biological circuits: Part 2
x organisms.Patterning by morphogen gradients is achieved by diffusing molecules sensed by biochemical circuitry, raising the question of the sensitivCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2ct to a broad variety of genetic and environmental perturbations (Waddington, 1959; von Dassow et al., 2000; Wilkins, 2001; Eldar et al., 2004). Tile most variable biochemical parameter in many systems is, as we have mentioned previously, the production rates of proteins. Experiments show that chang Ebook An introduction to systems biology design principles of biological circuits: Part 2ing the rate of morphogen production often leads to very little change in the sizes and positions of the regions formed. For example, a classic experiEbook An introduction to systems biology design principles of biological circuits: Part 2
mental approach shows that in many systems the patterning is virtually unchanged upon a twofold reduction in morphogen production, generated by mutatiCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2generate precise long-range patterns that are robust to such perturbations, following the work of Naama Barkai and her colleagues (Eldar et al., 2002, 2003, 2004). We will see that the most generic patterning mechanisms are not robust. Requiring robustness leads to special and rather elegant biochem Ebook An introduction to systems biology design principles of biological circuits: Part 2ical mechanisms.8.2EXPONENTIAL MORPHOGEN PROFILES ARE NOT ROBUSTLet us begin with the simplest mechanism, in which morphogen is produced al a source lEbook An introduction to systems biology design principles of biological circuits: Part 2
ocated al X - 0 and diffuses into a held of identical cells. The morphogen is degraded al rate a. We will see that the combination of diffusion and deCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2diffusion-degradation equation. In this equation, the diffusion term, D d' M/d x’, seeks to smooth out spatial variations in morphogen concentrations. The larger the diffusion constant D, the stronger the smoothing effect. Tile degradation of morphogen is described by a linear term -a M, resulting i Ebook An introduction to systems biology design principles of biological circuits: Part 2n an equation that relates the rale of change of M to its diffusion and degradation:d M/d t = D a2 M/d X2 - a M(8.2.1)To solve this diffusion-degradatEbook An introduction to systems biology design principles of biological circuits: Part 2
ion equation in a given region, we need to consider the values of M at the boundaries of the region. The boundary conditions are a steady concentratioCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2ogen molecules have been degraded.At steady-state (d M/d I = 0), Equation 8.2.1 becomes a linear ordinary differential equation:D d-’ M/d X2 - a M = 0And the solution is an exponential decay that results from a balance of the diffusion and degradation processes:M(x) = Moe-^(8.2.2)Thus, the morphogen Ebook An introduction to systems biology design principles of biological circuits: Part 2 level is highest at the source at X - 0, and decays with distance into the field. Hie decay is characterized by a decay length X:À = ựl)/a(8.2.3)HieEbook An introduction to systems biology design principles of biological circuits: Part 2
decay length X is the typical distance that a morphogen molecule travels into the field before it is degraded. The larger the diffusion constant D andCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2oncentration drops to about 5% and 5-10 5 of its initial162 ■ CHAPTER 8Position, XFIGURE 8.2 Changes in steady-state morphogen profile and the resulting pattern boundary upon a twofold reduction in morphogen concentration at X = 0. denoted Mo. The pattern boundary, defined by the position where M(x) Ebook An introduction to systems biology design principles of biological circuits: Part 2 equals the threshold T, shifts to the left by 0 when Mo is reduced to M„'.value. Roughly speaking, X is the typical size of the regions that can be pEbook An introduction to systems biology design principles of biological circuits: Part 2
atterned with such a gradient.The fate of each of the cells in the field is determined by the concentration of M at the cell’s position: the cell fateCHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process in Ebook An introduction to systems biology design principles of biological circuits: Part 2en by MfxJ = T, or, using Equation 8.2.2,xo= X log (Mo/T)(8.2.4)What happens if the production rate of the morphogen source is perturbed, so that the concentration of morphogen at the source Mo is replaced by Mo'? Equation 8.2.4 suggests that the position of the boundary shifts to xo' = X log (MO7T) Ebook An introduction to systems biology design principles of biological circuits: Part 2. The difference between the original and the shifted boundary is (Figure 8.2)ỗ = xo'-xo = Xlog(Mo7M<>)(8.2.5)CHAPTER 8Robust Patterning in Development8.1INTRODUCTION______________________________________________________Development is the remarkable process inGọi ngay
Chat zalo
Facebook