Limits...
Theoretical and experimental approaches to understand morphogen gradients.

Ibañes M, Izpisúa Belmonte JC - Mol. Syst. Biol. (2008)

Bottom Line: The mechanisms of morphogen transport and conversion from graded information to binary responses are some of the topics on which these combined strategies have shed light.In addition, we discuss those cases in which gradient formation and gradient interpretation at the molecular and/or cellular level may influence each other within a mutual feedback loop.To understand this interplay and the features it yields, it becomes essential to take system-level approaches that combine experimental and theoretical strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Estructura i Constituents de la Matèria, University of Barcelona, Barcelona, Spain.

ABSTRACT
Morphogen gradients, which specify different fates for cells in a direct concentration-dependent manner, are a highly influential framework in which pattern formation processes in developmental biology can be characterized. A common analysis approach is combining experimental and theoretical strategies, thereby fostering relevant data on the dynamics and transduction of gradients. The mechanisms of morphogen transport and conversion from graded information to binary responses are some of the topics on which these combined strategies have shed light. Herein, we review these data, emphasizing, on the one hand, how theoretical approaches have been helpful and, on the other hand, how these have been combined with experimental strategies. In addition, we discuss those cases in which gradient formation and gradient interpretation at the molecular and/or cellular level may influence each other within a mutual feedback loop. To understand this interplay and the features it yields, it becomes essential to take system-level approaches that combine experimental and theoretical strategies.

Show MeSH
Dynamics and steady state of morphogen gradients. (A) Morphogen gradients specify a pattern in a field of cells. (Left) All cells (yellow big circles) are equivalent and a morphogen gradient is set (small green circles). Over time (blue arrow), cells respond directly to the graded concentration of a secreted molecule and a pattern (right) is specified. (Right) Depending on the amount of graded signal, distinct genes become expressed within cells (represented by different colours inside cells) and different cellular behaviours are elicited (represented by different shapes of cells). (B) Bicoid, Dpp and Wingless gradients are represented by exponential profiles with their corresponding characteristic length (L). M stands for the morphogen level and x for the spatial position. (C) Transient (T) and steady-state (ST) gradients for two different molecules (simulating Dpp in red and a molecule X in green) that have different diffusion and degradation rates but the same characteristic length in the steady-state profile (L=20 μm). Transient gradients are computed at the same time point but, as shown, are distinct. Red curves were obtained by using the diffusion and degradation rates of Dpp. Green curves were computed by setting the molecular half-life eight times shorter than that of Dpp and the diffusion rate eight times larger. (D) Shape of the gradient profile at a transient time (T) and at the steady state (ST) in logarithmic spatial scale for parameter values of Dpp. The features of the gradients at the two time points are very distinct. In panels B and C, the morphogen level has been scaled such that the steady state has a morphogen level of 1 at the source (x=0). Profiles in panels C and D have been computed numerically according to ∂M(x,t)/∂t=α∂(x)+D∂2M/∂x2−βM with an impermeable wall at x=0.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2290935&req=5

f1: Dynamics and steady state of morphogen gradients. (A) Morphogen gradients specify a pattern in a field of cells. (Left) All cells (yellow big circles) are equivalent and a morphogen gradient is set (small green circles). Over time (blue arrow), cells respond directly to the graded concentration of a secreted molecule and a pattern (right) is specified. (Right) Depending on the amount of graded signal, distinct genes become expressed within cells (represented by different colours inside cells) and different cellular behaviours are elicited (represented by different shapes of cells). (B) Bicoid, Dpp and Wingless gradients are represented by exponential profiles with their corresponding characteristic length (L). M stands for the morphogen level and x for the spatial position. (C) Transient (T) and steady-state (ST) gradients for two different molecules (simulating Dpp in red and a molecule X in green) that have different diffusion and degradation rates but the same characteristic length in the steady-state profile (L=20 μm). Transient gradients are computed at the same time point but, as shown, are distinct. Red curves were obtained by using the diffusion and degradation rates of Dpp. Green curves were computed by setting the molecular half-life eight times shorter than that of Dpp and the diffusion rate eight times larger. (D) Shape of the gradient profile at a transient time (T) and at the steady state (ST) in logarithmic spatial scale for parameter values of Dpp. The features of the gradients at the two time points are very distinct. In panels B and C, the morphogen level has been scaled such that the steady state has a morphogen level of 1 at the source (x=0). Profiles in panels C and D have been computed numerically according to ∂M(x,t)/∂t=α∂(x)+D∂2M/∂x2−βM with an impermeable wall at x=0.

Mentions: Embryonic development involves spatial and temporal patterns of cellular differentiation and the shaping of form. How do embryonic tissues organize in space and time such that a field of distinct cells emerges reliably? This question has fascinated developmental biologists for decades. Early in the last century, the existence of gradients that could signal over large distances was proposed to account for patterning (Morgan, 1901). Indeed, morphogen gradients, defined as graded distributions of secreted molecules that specify distinct fates for the cells in a concentration-dependent and direct manner (Wolpert, 1969), have become, over the last few decades, a highly influential framework to test and understand pattern formation processes during embryonic development (Figure 1A).


Theoretical and experimental approaches to understand morphogen gradients.

Ibañes M, Izpisúa Belmonte JC - Mol. Syst. Biol. (2008)

Dynamics and steady state of morphogen gradients. (A) Morphogen gradients specify a pattern in a field of cells. (Left) All cells (yellow big circles) are equivalent and a morphogen gradient is set (small green circles). Over time (blue arrow), cells respond directly to the graded concentration of a secreted molecule and a pattern (right) is specified. (Right) Depending on the amount of graded signal, distinct genes become expressed within cells (represented by different colours inside cells) and different cellular behaviours are elicited (represented by different shapes of cells). (B) Bicoid, Dpp and Wingless gradients are represented by exponential profiles with their corresponding characteristic length (L). M stands for the morphogen level and x for the spatial position. (C) Transient (T) and steady-state (ST) gradients for two different molecules (simulating Dpp in red and a molecule X in green) that have different diffusion and degradation rates but the same characteristic length in the steady-state profile (L=20 μm). Transient gradients are computed at the same time point but, as shown, are distinct. Red curves were obtained by using the diffusion and degradation rates of Dpp. Green curves were computed by setting the molecular half-life eight times shorter than that of Dpp and the diffusion rate eight times larger. (D) Shape of the gradient profile at a transient time (T) and at the steady state (ST) in logarithmic spatial scale for parameter values of Dpp. The features of the gradients at the two time points are very distinct. In panels B and C, the morphogen level has been scaled such that the steady state has a morphogen level of 1 at the source (x=0). Profiles in panels C and D have been computed numerically according to ∂M(x,t)/∂t=α∂(x)+D∂2M/∂x2−βM with an impermeable wall at x=0.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2290935&req=5

f1: Dynamics and steady state of morphogen gradients. (A) Morphogen gradients specify a pattern in a field of cells. (Left) All cells (yellow big circles) are equivalent and a morphogen gradient is set (small green circles). Over time (blue arrow), cells respond directly to the graded concentration of a secreted molecule and a pattern (right) is specified. (Right) Depending on the amount of graded signal, distinct genes become expressed within cells (represented by different colours inside cells) and different cellular behaviours are elicited (represented by different shapes of cells). (B) Bicoid, Dpp and Wingless gradients are represented by exponential profiles with their corresponding characteristic length (L). M stands for the morphogen level and x for the spatial position. (C) Transient (T) and steady-state (ST) gradients for two different molecules (simulating Dpp in red and a molecule X in green) that have different diffusion and degradation rates but the same characteristic length in the steady-state profile (L=20 μm). Transient gradients are computed at the same time point but, as shown, are distinct. Red curves were obtained by using the diffusion and degradation rates of Dpp. Green curves were computed by setting the molecular half-life eight times shorter than that of Dpp and the diffusion rate eight times larger. (D) Shape of the gradient profile at a transient time (T) and at the steady state (ST) in logarithmic spatial scale for parameter values of Dpp. The features of the gradients at the two time points are very distinct. In panels B and C, the morphogen level has been scaled such that the steady state has a morphogen level of 1 at the source (x=0). Profiles in panels C and D have been computed numerically according to ∂M(x,t)/∂t=α∂(x)+D∂2M/∂x2−βM with an impermeable wall at x=0.
Mentions: Embryonic development involves spatial and temporal patterns of cellular differentiation and the shaping of form. How do embryonic tissues organize in space and time such that a field of distinct cells emerges reliably? This question has fascinated developmental biologists for decades. Early in the last century, the existence of gradients that could signal over large distances was proposed to account for patterning (Morgan, 1901). Indeed, morphogen gradients, defined as graded distributions of secreted molecules that specify distinct fates for the cells in a concentration-dependent and direct manner (Wolpert, 1969), have become, over the last few decades, a highly influential framework to test and understand pattern formation processes during embryonic development (Figure 1A).

Bottom Line: The mechanisms of morphogen transport and conversion from graded information to binary responses are some of the topics on which these combined strategies have shed light.In addition, we discuss those cases in which gradient formation and gradient interpretation at the molecular and/or cellular level may influence each other within a mutual feedback loop.To understand this interplay and the features it yields, it becomes essential to take system-level approaches that combine experimental and theoretical strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Estructura i Constituents de la Matèria, University of Barcelona, Barcelona, Spain.

ABSTRACT
Morphogen gradients, which specify different fates for cells in a direct concentration-dependent manner, are a highly influential framework in which pattern formation processes in developmental biology can be characterized. A common analysis approach is combining experimental and theoretical strategies, thereby fostering relevant data on the dynamics and transduction of gradients. The mechanisms of morphogen transport and conversion from graded information to binary responses are some of the topics on which these combined strategies have shed light. Herein, we review these data, emphasizing, on the one hand, how theoretical approaches have been helpful and, on the other hand, how these have been combined with experimental strategies. In addition, we discuss those cases in which gradient formation and gradient interpretation at the molecular and/or cellular level may influence each other within a mutual feedback loop. To understand this interplay and the features it yields, it becomes essential to take system-level approaches that combine experimental and theoretical strategies.

Show MeSH