Maternal effects can adaptively modulate offspring developmental trajectories in variable but predictable environments. Hormone synthesis is sensitive to environmental factors, and maternal hormones are thus a powerful mechanism to transfer environmental cues to the next generation. Birds have become a key model for the study of hormone-mediated maternal effects because the embryo develops outside the mother's body, facilitating the measurement and manipulation of prenatal hormone exposure. At the same time, birds are excellent models for the integration of both proximate and ultimate approaches, which is key to a better understanding of the evolution of hormone-mediated maternal effects. Over the past two decades, a surge of studies on hormone-mediated maternal effects has revealed an increasing number of discrepancies. In this review, we discuss the role of the environment, genetic factors and social interactions in causing these discrepancies and provide a framework to resolve them. We also explore the largely neglected role of the embryo in modulating the maternal signal, as well as costs and benefits of hormone transfer and expression for the different family members. We conclude by highlighting fruitful avenues for future research that have opened up thanks to new theoretical insights and technical advances in the field. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

Bacterial cell division is mediated by a multi-protein machine known as the “divisome”, which assembles at the site of cell division. Formation of the divisome starts with the polymerization of the tubulin-like protein FtsZ into a ring, the Z-ring. Z-ring formation is under tight control to ensure bacteria divide at the right time and place. Several proteins bind to the Z-ring to mediate its membrane association and persistence throughout the division process. A conserved stretch of amino acids at the C-terminus of FtsZ appears to be involved in many interactions with other proteins. Here, we describe a novel pull-down assay to look for binding partners of the FtsZ C-terminus, using a HaloTag affinity tag fused to the C-terminal 69 amino acids of B. subtilis FtsZ. Using lysates of Escherichia coli overexpressing several B. subtilis cell division proteins as prey we show that the FtsZ C-terminus specifically pulls down SepF, but not EzrA or MinC, and that the interaction depends on a conserved 16 amino acid stretch at the extreme C-terminus. In a reverse pull-down SepF binds to full-length FtsZ but not to a FtsZΔC16 truncate or FtsZ with a mutation of a conserved proline in the C-terminus. We show that the FtsZ C-terminus is required for the formation of tubules from FtsZ polymers by SepF rings. An alanine-scan of the conserved 16 amino acid stretch shows that many mutations affect SepF binding. Combined with the observation that SepF also interacts with the C-terminus of E. coli FtsZ, which is not an in vivo binding partner, we propose that the secondary and tertiary structure of the FtsZ C-terminus, rather than specific amino acids, are recognized by SepF.

Vertebrate embryos are exposed to maternal hormones that can profoundly affect their later phenotype. Although it is known that the embryo can metabolize these maternal hormones, the metabolic outcomes, their quantitative dynamics and timing are poorly understood. Moreover, it is unknown whether embryos can adjust their metabolic activity to, for example, hormones or other maternal signals. We studied the dynamics of maternal steroids in fertilized and unfertilized rock pigeon eggs during early incubation. Embryos of this species are naturally exposed to different amounts of maternal steroids in the egg according to their laying position, which provides a natural context to study differential embryonic regulation of the maternal signals. We used mass spectrometric analyses to map changes in the androgen and estrogen pathways of conversion. We show that the active hormones are heavily metabolized only in fertilized eggs, with a corresponding increase in supposedly less potent metabolites already within one-fourth of total incubation period. Interestingly, the rate of androgen metabolism was different between embryos in different laying positions. The results also warrant a re-interpretation of the timing of hormone mediated maternal effects and the role of the supposedly biologically inactive metabolites. Furthermore, the results also provide a potential solution as to how the embryo can prevent maternal steroids in the egg from interfering with its sexual differentiation processes as we show that the embryo can metabolize most of the maternal steroids before sexual differentiation starts.

The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic downshock. Sensing bilayer tension, MscL channels are sensitive to changes in the bilayer environment and are, therefore, an ideal test case for exploring membrane protein coupling. Here, we use high-throughput coarse-grained molecular dynamics simulations to characterize MscL gating kinetics in different bilayer environments under the influence of alcohols. We performed over five hundred simulations to obtain sufficient statistics to reveal the subtle effects of changes in the membrane environment on MscL gating. MscL opening times were found to increase with the addition of the straight-chain alcohols ethanol, octanol, and to some extent dodecanol but not with hexadecanol. Increasing concentration of octanol increased the impeding effect, but only up to 10–20 mol %. Our in silico predictions were experimentally confirmed using reconstituted MscL in a liposomal fluorescent efflux assay. Our combined data reveal that the effect of alcohols on MscL gating arises not through specific binding sites but through a combination of the alcohol-induced changes to a number of bilayer properties and their alteration of the MscL–bilayer interface. Our work provides a key example of how extensive molecular simulations can be used to predict the functional modification of membrane proteins by subtle changes in their bilayer environment.

Several studies show effects of yolk androgens in avian eggs on the phenotype of the offspring. Yolk hormone concentrations decline strongly within the first few days of incubation. Although early embryonic uptake of yolk androgens is suggested by the presence of radioactivity in the embryo when eggs are injected with radiolabelled androgens, these studies do not verify the chemical identity of radioactive compound(s), although it is known that these androgens can be metabolized substantially. By using stable isotopelabelled testosterone and androstenedione in combination with mass spectrometry, enabling verification of the exact molecular identity of labelled compounds in the embryo, we found that after 5 days of incubation the androgens were not taken up by the embryo. However, their concentrations in the entire yolk albumen homogenates declined strongly, even when corrected for dilution by albumen and water. Our results indicate metabolism of maternal androgens, very likely to 5βandrostane-3α,17β-diol, etiocholanolone and their conjugated forms. The results imply that the effects of increased exposure of the embryo to maternal androgens take place either before this early conversion or are mediated by these metabolites with an as yet unknown function, opening new avenues for understanding hormone-mediated maternal effects in vertebrates.