The Bicoid Morphogen System

Abstract

Several fundamental concepts of developmental biology have emerged from studies on the early development of the Drosophila melanogaster embryo. In the late 1980s, studies on Bicoid provided the first solid experimental evidence for the existence of morphogenetic gradients and their implication in axial patterning. Bicoid has since stimulated further research, bringing together developmental and cell biologists, physicists and theoreticians to address fundamental biological questions. These include mechanistic aspects of transcriptional and translational control, molecular and functional aspects of evolution and, more recently with the development of quantitative approaches, the robustness of axial patterning in a systems biology view. However, recent studies provide data which lead to contradictory interpretations. Here, we discuss these recent observations, highlighting the data helping to understand how anterior patterning is achieved under the control of Bicoid and point to novel challenges for future studies.

New Model for Understanding Mechanisms of Biological Signaling: Direct Transport via Cytonemes

“…It is now widely accepted that the central role in the biological development, that leads to a complex spatio-temporal patterning in living systems, is played by multiple signaling molecules or morphogens. [1][2][3][4][5] These biological signaling molecules develop non-uniform concentration profiles, known as morphogen gradients. Embryo cells interact with morphogens, and different genes are activated or suppressed depending on the local concentration of signaling molecules.…”

“…1,2,4 A large number of experimental and theoretical investigations on the formation and functioning of morphogen gradients has appeared in recent years. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]21,22 However, many aspects of biological signaling remain not well understood. 4,6 One of the most important problems of the biological development is to understand the mechanisms of the morphogen gradients formation.…”

“…The SDD mechanism predicts the exponentially decaying signaling profiles, which qualitatively agrees with many experimental observations. 4,5,[8][9][10] Despite common use of the SDD model and related approaches for many biological systems, there is a growing number of experimental observations, suggesting that the indirect delivery of the morphogens via diffusion might not be the only mechanism in the transportation of morphogenetic signals. 6,22,23,34 It has been argued that the complex environment of the embryo systems might prevent the passive free diffusion from establishing distinguishable morphogen gradients at different regions.…”

“…The advantage of using cytonemes to deliver the morphogenetic signaling molecules is that they can easily adapt to a complex topography of embryo systems, providing a much more precise transfer of information to underlying cells. 6 N 2 1 0 While various theoretical models have been proposed to describe the formation of the morphogen gradients via free extracellular diffusion, 5,[16][17][18][19] there is no detailed theoretical framework for analyzing the direct delivery mechanism (although one should mention recent quantitative studies presented in Ref. 20 ).…”

“…The exponential morphogen gradients are also found for the indirect free diffusion delivery of the signaling molecules at large times. 5,6,16 However, in this case the decay length is determined by the ratio of diffusion and degradation rates. 14,16 This underlies the importance of energy dissipation in the transportation of signaling molecules through cytonemes.…”