Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis
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Embryogenesis relies on instructions provided by spatially organized signaling molecules known as morphogens. Understanding the principles behind morphogen distribution and how cells interpret locally this information remains a major challenge in developmental biology.
Acquisition of different cell fates at specific spatial and temporal locations is an essential process driving development. The necessary information is provided locally by morphogens (Wolpert, 1969; Lander, 2011). Understanding morphogen gradient formation requires systematic measurement of the morphogen abundance, mobility, and distribution using temporally resolved methods. However, the technical challenges associated with this undertaking are high, leading to significant discussions on how to best assess the principles and mechanisms (Ribes & Briscoe, 2009; Rogers & Schier, 2011; Muller et al, 2013) that have resulted in a plethora of models for the formation of morphogen gradients.
The classic view of Bcd gradient formation is that the protein is synthesized in the anterior pole of the Drosophila blastoderm and forms a long range gradient through diffusion, with the gradient shape adapted by protein degradation
However, several other models involving alternative mechanisms for Bcd production and distribution have been proposed, all of which are capable of producing an exponential‐like concentration profile, as further outlined below
Efforts to distinguish experimentally the different mechanisms of gradient formation have been hindered by uncertainties associated with the measurements of the relevant parameters: local production rates of Bcd; Bcd mobility and transport; and Bcd degradation.
Finally, the extent of the region where Bcd protein is produced is unclear
Altogether, these debates regarding nearly every aspect of Bcd gradient formation argue for the need of more incisive tools to investigate this paradigmatic problem.
How does the Bcd gradient form?
an mRNA gradient plays only a limited role in Bcd protein gradient formation.
Changes in protein levels can be caused by regulation of their synthesis or their degradation.
Bcd production is reduced during cycle 14, probably due to degradation of its mRNA or cellularization.
The underlying mechanisms driving the time dependence in the kinetic parameters could be due to a number of (potentially inter‐related) factors.
the embryo must be interpreting a dynamic gradient at all times.
more complicated modes of interpretation—likely via spatial and temporal integration through the downstream gap gene network—are essential for reliable interpretation of the Bcd concentration gradient into precise positional information
understanding of developmental patterning requires access to both spatial and temporal information
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