Probing Intrinsic Properties of a Robust Morphogen Gradient in Drosophila

Abstract

A remarkable feature of development is its reproducibility, the ability to correct embryo-to-embryo variations and instruct precise patterning. In Drosophila, embryonic patterning along the anterior-posterior axis is controlled by the morphogen gradient Bicoid (Bcd). In this report, we describe quantitative studies of the native Bcd gradient and its target Hunchback (Hb). We show that the native Bcd gradient is highly reproducible and is itself scaled with embryo length. While a precise Bcd gradient is necessary for precise Hb expression, it still has positional errors greater than Hb expression. We describe analyses further probing mechanisms for Bcd gradient scaling and correction of its residual positional errors. Our results suggest a simple model of a robust Bcd gradient sufficient to achieve scaled and precise activation of its targets. The robustness of this gradient is conferred by its intrinsic properties of "self-correcting" the inevitable input variations to achieve a precise and reproducible output.

Morphogen gradient formation and action

“…17). Figure 2B shows that our simulated [B n ] profile and experimentally measured Bcd profile, 23 both at early nuclear cycle 14, exhibit strong resemblance to each other. These and additional results (below) show that our biologically realistic model can recapitulate key properties of the Bcd gradient.…”

“…two separate cases where mutant embryos exhibit increased variability in the hunchback (hb) expression boundary, we were able to trace the origin of such variability directly to perturbed Bcd gradient properties. 23,35 To our knowledge, these results represent the only experimental evidence that a precise Bcd gradient is necessary for precise developmental decisions. Our finding 1 that the shift in Bcd-encoded positional information in fsd embryos matches the shift in hb expression boundary further underscores a direct and dominant role of Bcd in instructing hb expression (see also ref.…”

“…For example, it also readily explains the differences in Bcd gradient profiles caused by the geometric asymmetry between the dorsal and ventral sides of the embryo. 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.…”

“…18,[29][30][31][32][33] However, more recent studies revealed that the Bcd gradient profile is highly precise among different embryos. 23,34,35 But whether a precise Bcd gradient is important for precise patterning remains controversial. It was suggested that, based on thermal perturbations, a precise Bcd gradient is not required for precise patterning.…”

Anterior-posterior positional information in the absence of a strong Bicoid gradient

“…Intense efforts have been expended to determine whether the Bcd gradient is the primary determinant that positions and sharpens the posterior boundary of the zygotic expression domain of the target gene hunchback (hb) (5)(6)(7)(8). However, a complete understanding of anterior patterning will require the identification of all target genes activated by the Bcd morphogen, and the elucidation of the mechanisms that position each one.…”