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Decapentaplegic has long been thought to be a morphogen that controls patterning and growth in Drosophila wings, but hard evidence for the requisite long-range action has only now come from two new studies.

Dpp, a member of the BMP family, is a morphogen that specifies positional information in Drosophila wing precursors. In this tissue, Dpp expressed along the anterior-posterior boundary forms a concentration gradient that controls the expression domains of target genes, which in turn specify the position of wing veins. Dpp also promotes growth in this tissue. The relationship between the spatio-temporal profile of Dpp signalling and growth has been the subject of debate, which has intensified recently with the suggestion that the stripe of Dpp is dispensable for growth. With two independent conditional alleles of dpp, we find that the stripe of Dpp is essential for wing growth. We then show that this requirement, but not patterning, can be fulfilled by uniform, low level, Dpp expression. Thus, the stripe of Dpp ensures that signalling remains above a pro-growth threshold, while at the same time generating a gradient that patterns cell fates. DOI: http://dx.doi.org/10.7554/eLife.22546.001, eLife digest From the wings of a butterfly to the fingers of a human hand, living tissues often have complex and intricate patterns. Developmental biologists have long been fascinated by the signals – called morphogens – that guide how these kinds of pattern develop. Morphogens are substances that are produced by groups of cells and spread to the rest of the tissue to form a gradient. Depending on where they sit along this gradient, cells in the tissue activate different sets of genes, and the resulting pattern of gene activity ultimately defines the position of the different parts of the tissue. Decades worth of studies into how limbs develop in animals from mice to fruit flies have revealed common principles of morphogen gradients that regulate the development of tissue patterns. Morphogens have been shown to help regulate the growth of tissues in a number of different animals as well. However, how the morphogens regulate tissue size and what role their gradients play in this process remain topics of intense debate in the field of developmental biology. In the developing wing of a fruit fly, a morphogen called Dpp is expressed in a thin stripe located in the centre and spreads to the rest of the tissue to form a gradient. Bosch, Ziukaite, Alexandre et al. have now characterised where and when the Dpp morphogen must be produced to regulate both the final size of the fly’s wing and the number of cells the wing eventually contains. The experiments involved preventing the production of Dpp in the developing wing in specific cells and at specific stages of development. This approach confirmed that Dpp must be produced in the central stripe for the wing to grow. Matsuda and Affolter and, independently, Barrio and Milán report the same findings in two related studies. Moreover, Bosch et al. and Barrio and Milán also conclude that the gradient of Dpp throughout the wing is not required for growth. Further work will be needed to explain how the Dpp signal regulates the growth of the wing. The answer to this question will contribute to a better understanding of the role of morphogens in regulating the size of human organs and how a failure to do so might cause developmental disorders. DOI: http://dx.doi.org/10.7554/eLife.22546.002

Department of Chemical and Biological Engineering andLewis-Sigler Institute for Integrative Genomics, PrincetonUniversity, Princeton, NJ 08544, USASummaryZygotic genome activation (ZGA) is a major genome pro-gramming event whereby the cells of the embryo begin toadopt specified fates. Experiments in Drosophila and zebra-fishhaverevealedthatZGAdependsontranscriptionfactorsthatprovidelarge-scalecontrolofgeneexpressionbydirectand specific binding to gene regulatory sequences [1–5].Zelda(Zld)playssucharoleintheDrosophilaembryo,whereit has been shown to control the action of patterning signals[1, 2]; however, the mechanisms underlying this effectremain largely unclear. A recent model proposed that Zldbinding sitesactasquantitative regulators ofthespatiotem-poral expression of genes activated by Dorsal (Dl), themorphogen that patterns the dorsoventral axis [6]. Here wetestedthismodelexperimentally,usingenhancersofbrinker(brk) and short gastrulation (sog), both of which are directlyactivated by Dl, but at different concentration thresholds[7–9]. In agreement with the model, we show that there is aclearpositivecorrelationbetweenthenumberofZldbindingsites and the spatial domain of enhancer activity. Likewise,the timing of expression could be advanced or delayed. Wepresent evidence that Zld facilitates binding of Dl to regula-tory DNA, and that this is associated with increased chro-matin accessibility. Importantly, the change in chromatinaccessibility is strongly correlated with the change in Zldbinding, but not Dl. We propose that the ability of genomeactivators to facilitate readout of transcriptional input iskey to widespread transcriptional induction during ZGA.Results and DiscussionInblastodermembryos,brinker(brk)isactivatedinaneight-toten-cell-widedomainthatdevelopsintotheventralneurogenicectoderm (NE), whereas short gastrulation (sog) is expressedin a broader band of 16–18 cells encompassing the entire NE(see Figures 1A and 1I). Both genes have the same ventralexpression boundary due to repression by Snail (Sna) in thepresumptive mesoderm [11–15]. The dorsal borders of theirdomains lie in regions of the Dorsal (Dl) gradient whereamounts are low and change little, raising the question ofhow their enhancers can interpret small differences in Dlconcentrations.sog and brk each have two reported cis-regulatory modules(enhancers) that are active in early embryos [10, 16–20]. Thesog intronic lateral stripe enhancer (LSE) [16] is less wellconserved and drives a slightly narrower stripe of expressionrelative to the sog shadow enhancer [17], also known as theneurogenic ectoderm enhancer (NEE), which recapitulatesthe broad endogenous sog pattern [18]. The brk 5