Seeing is believing: the Bicoid protein reveals its path

Abstract

In this commentary, I will review the latest findings on the Bicoid (Bcd) morphogen in Drosophila, a paradigm for gradient formation taught to biology students for more than two decades. “Seeing is believing” also summarizes the erroneous steps that were needed to elucidate the mechanisms of gradient formation and the path of movement of Bcd. Initially proclaimed as a dogma in 1988 and later incorporated into the SDD model where the broad diffusion of Bcd throughout the embryo was the predominant step leading to gradient formation, the SDD model was irrefutable for more than two decades until first doubts were raised in 2007 regarding the diffusion properties of Bcd associated with the SDD model. This led to re-thinking of the issue and the definition of a new model, termed the ARTS model which could explain most of the physical constraints that were inherently associated with the SDD model. In the ARTS model, gradient formation is mediated by the mRNA which is redistributed along cortical microtubules to form a mRNA gradient which is translated to form the protein gradient. Contrary to the SDD model, there is no Bcd diffusion from the tip. The ARTS model is also compatible with the observed cortical movement of Bcd. I will critically compare the SDD and the ARTS models as well as other models, analyze the major differences, and highlight the path where Bcd is localized during early nuclear cycles.

bicoid RNA localization requires the trans-Golgi network

“…Our study provides evidence that the simple SDD diffusion model proposed more than 3 decades ago by [1] needs to be revised in order to explain the movement of Bcd for gradient formation [8]. Our data demonstrates that the bcd mRNA gradient is the template for the Bcd protein gradient, also termed the ARTS model [9, 10].…”

“…Recently, a newly-assembled omnidirectional MT network and a motor for bcd mRNA transport was detected at the cortex of early staged embryos [10] fulfilling all the criteria for a transportation system that was predicted [9]. To conclude, active bcd mRNA transport as the primary step for Bcd protein gradient formation is now widely accepted, and consistent with the observation of subtle Bcd protein movement along the cortex [7, 8].…”

“…These were proposed to be sufficiently high enough to explain the SDD model. In contrast, a recent report showed that Bcd does not move in a broad front through the egg, as the SDD model predicts [7, 8], rather it moved along the cortex, as did the mRNA. This data, based on simple experiments immediately refuted the SDD model because it showed that the assumptions of the protein diffusing in a broad front were erroneous.…”

“…Here, the formation of the Bcd gradient is based on the existence of a mRNA gradient, mediated by active transport of the mRNA along microtubules (MTs) which exhibits the same variability in shape. This constituted a fourth explanation which resolved most of the constraints that were inherent with the SDD model, reviewed by [8]. Quantitative assays of bcd mRNA and Bcd-GFP protein in real-time indicated that the graded mRNA movement made an essential contribution to generating the protein gradient [11].…”

Modulating the bicoid gradient in space and time

“…The formation of the Bicoid (Bcd) gradient in Drosophila is one of the most fascinating observations in biology that has intrigued scientists for many decades [ 1 ]. Originally discovered as a Drosophila mutant that affects anterior patterning of the early egg [ 2 ], the remarkable Bcd protein gradient became the hallmark that served as paradigm for gradient formation in science for almost three decades [ 3 ].…”