Scaling of the Bicoid morphogen gradient by a volume-dependent production rate

Abstract

SUMMARYAn important feature of development is the formation of patterns that are proportional to the overall size of the embryo. But how such proportionality, or scaling, is achieved mechanistically remains poorly understood. Furthermore, it is currently unclear whether organisms utilize similar or distinct mechanisms to achieve scaling within a species and between species. Here we investigate within-species scaling mechanisms for anterior-posterior (A-P) patterning in Drosophila melanogaster, focusing specifically on the properties of the Bicoid (Bcd) morphogen gradient. Using embryos from lines artificially selected for large and small egg volume, we show that large embryos have higher nuclear Bcd concentrations in the anterior than small embryos. This anterior difference leads to scaling properties of the Bcd gradient profiles: in broad regions of the large and small embryos along the A-P axis, normalizing their positions to embryo length reduces the differences in both the nuclear Bcd concentrations and Bcd-encoded positional information. We further trace the origin of Bcd gradient scaling by showing directly that large embryos have more maternally deposited bcd mRNA than small embryos. Our results suggest a simple model for how within-species Bcd gradient scaling can be achieved. In this model, the Bcd production rate, which is dependent on the total number of bcd mRNA molecules in the anterior, is scaled with embryo volume.

Morphogen gradient formation and action

“…22 In addition, it recapitulates the scaling properties of the Bcd gradient 23 by simply assuming a correlation between the Bcd production rate and embryo volume. 12 This hypothesized correlation was recently observed experimentally 13 through quantitative measurements of bcd mRNA in large and small embryos from selected Drosophila lines. 24 Since our model is based on Bcd diffusion and degradation while incorporating relevant, biologically realistic features of the embryo, our results suggest that the diffusion model-despite the inadequacies of its idealized form in fully capturing Bcd gradient properties-remains a .…”

“…51 Importantly, the scaling properties of hb can also be traced directly to the scaling properties of the Bcd gradient. 12,13,23 These and other results have led us to propose in reference 23 that the Bcd gradient itself is a robust system (see also refs. 34 and 49).…”

Scale invariance of morphogen-mediated patterning by flux optimization

“…Taking the data from Cheung et al with ( / ) 1/2 = 99 microns [5], assuming = 0.4 is the spatial location where the critical threshold is crossed in the embryo (near the Hunchback boundary), and using = 645 for the large embryo and 0 = 518 for the small embryo, the calculated optimal flux is 67% greater in the large embryo than the flux in the small embryo 0 . This is remarkably close to the increase in amplitude measured for Bcd scaling of 66.9% .…”

“…Recently Cheung et al, [5] investigated the spatial patterns of Bcd patterning between artificially selected populations of an initially wild type Drosophila melanogaster. After successive rounds of selection, two populations were developed that differed in egg length by about 25%.…”

Transcriptional activators and activation mechanisms

“…The Drosophila activator Bicoid (Bcd) forms a concentration gradient in early embryos and instructs anterior-posterior patterning (Grimm et al, 2010;Lohr et al, 2010;. It offers an excellent system for studying transcriptional activation mechanisms in both space and time (Gregor et al, 2007a, b;He et al, 2008;Deng et al, 2010;He et al, 2010a, b;Cheung et al, 2011;. A recently reported method of simultaneously, and quantitatively, detecting Bcd and the nascent transcripts of its target genes in early Drosophila embryos made it possible to evaluate the role of this activator in the actual events of transcriptional bursts, as opposed to the accumulated products .…”