Adaptation of the length scale and amplitude of the Bicoid gradient profile to achieve robust patterning in abnormally large Drosophila melanogaster embryos

Abstract

The formation of patterns that are proportional to the size of the embryo is an intriguing but poorly understood feature of development. Molecular mechanisms controlling such proportionality, or scaling, can be probed through quantitative interrogations of the properties of morphogen gradients that instruct patterning. Recent studies of the Drosophila morphogen gradient Bicoid (Bcd), which is required for anterior-posterior (AP) patterning in the early embryo, have uncovered two distinct ways of scaling. Whereas between-species scaling is achieved by adjusting the exponential shape characteristic of the Bcd gradient profile, namely, its length scale or length constant (λ), within-species scaling is achieved through adjusting the profile's amplitude, namely, the Bcd concentration at the anterior (B 0 ). Here, we report a case in which Drosophila melanogaster embryos exhibit Bcd gradient properties uncharacteristic of their size. The embryos under investigation were from a pair of inbred lines that had been artificially selected for egg size extremes. We show that B 0 in the large embryos is uncharacteristically low but λ is abnormally extended. Although the large embryos have more total bcd mRNA than their smaller counterparts, as expected, its distribution is unusually broad. We show that the large and small embryos develop gene expression patterns exhibiting boundaries that are proportional to their respective lengths. Our results suggest that the large-egg inbred line has acquired compensating properties that counteract the extreme length of the embryos to maintain Bcd gradient properties necessary for robust patterning. Our study documents, for the first time to our knowledge, a case of within-species Bcd scaling achieved through adjusting the gradient profile's exponential shape characteristic, illustrating at a molecular level how a developmental system can follow distinct operational paths towards the goal of robust and scaled patterning.

Time to move on: Modeling transcription dynamics during an embryonic transition away from maternal control

“…3 This relatively reliable input-output relationship between Bcd and hb transcription has been suggested to be important for AP pattern formation in a manner that is robust to embryo size variations. 3,[34][35][36][37][38] The estimated parameters in our current study are consistent with existing estimates and yield new insights into transcription regulatory mechanism during embryonic development. For example, our estimated k on (prior to shutdown) and k off are both fast, as those at earlier nuclear cycles reported by Xu et al, 15 despite the significant differences in our experimental and modeling approaches.…”

Intracellular Scaling Mechanisms

“…Bicoid is synthesized from an anteriorly enriched local source of mRNA, leading to an exponential gradient extending to the posterior (Grimm et al 2010). Instead of scaling the gradient length scale as above, differently sized embryos show scaled gradient amplitude (He et al 2008;Cheung et al 2013). Consequently, in terms of absolute concentration, the gradient extends further from the anterior in large embryos.…”

Developmental Pattern Formation in Phases

“…However, partial scaling of pattern for some positions in the tissue can be achieved by adjusting the gradient amplitude (reviewed in [79]). For instance, in Drosophila melanogaster populations artificially selected for different sizes, the Bicoid (Bcd) gradient amplitude at nuclear cycle 14 scales with embryo volume and correlates with the amount of maternally deposited Bcd [80,81]. In these embryos, the volume varied by nearly 40%, while the relative anteroposterior positions of evenskipped (eve) boundaries were nearly identical [82].…”