@misc{leblanc_medlock_2015, title={Males on demand: the environmental-neuro-endocrine control of male sex determination in daphnids}, volume={282}, ISSN={["1742-4658"]}, DOI={10.1111/febs.13393}, abstractNote={Branchiopod crustaceans (e.g., Daphnia sp.) and some other taxa utilize both asexual and sexual reproduction to maximize population sustainability. The decision to switch from asexual to sexual reproduction is triggered by environmental cues that foretell a potentially detrimental change in environmental conditions. This review describes the cascade of events beginning with environmental cues and ending with changes in gene expression that dictate male sex determination in daphnids, the initial event in the switch to sexual reproduction. Several environmental cues have been identified which, either in isolation or in combination, stimulate male sex determination. These cues are typically associated with change of season, exhaustion of resources or loss of habitat. Maternal daphnids receive and respond to these cues, we propose, through the secretion of neuropeptides, which suppress (hyperglycemic hormone‐like neuropeptides, allatostatin) or stimulate (allatotropin) the male sex differentiation program. In response, maternal daphnids produce the male sex‐determining hormone, methyl farnesoate. Methyl farnesoate binds to a protein MET that dimerizes with the protein SRC forming an active transcription factor. This complex then regulates the expression of genes, primarily doublesex (dsx), involved in programming the single‐celled embryo to develop into a male. In the absence of methyl farnesoate programming, the embryo develops into a female. Epigenetic modifications of the genome as a possible mode of methyl farnesoate action and the utility of this model to decipher the role of epigenetics in sex differentiation in other species are discussed.}, number={21}, journal={FEBS JOURNAL}, author={LeBlanc, Gerald A. and Medlock, Elizabeth K.}, year={2015}, month={Nov}, pages={4080–4093} }
 @article{leblanc_wang_holmes_kwon_medlock_2013, title={A Transgenerational Endocrine Signaling Pathway in Crustacea}, volume={8}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0061715}, DOI={10.1371/journal.pone.0061715}, abstractNote={Background Environmental signals to maternal organisms can result in developmental alterations in progeny. One such example is environmental sex determination in Branchiopod crustaceans. We previously demonstrated that the hormone methyl farnesoate could orchestrate environmental sex determination in the early embryo to the male phenotype. Presently, we identify a transcription factor that is activated by methyl farnesoate and explore the extent and significance of this transgenerational signaling pathway. Methodology/Principal Findings Several candidate transcription factors were cloned from the water flea Daphnia pulex and evaluated for activation by methyl farnesoate. One of the factors evaluated, the complex of two bHLH-PAS proteins, dappuMet and SRC, activated a reporter gene in response to methyl farnesoate. Several juvenoid compounds were definitively evaluated for their ability to activate this receptor complex (methyl farnesoate receptor, MfR) in vitro and stimulate male sex determination in vivo. Potency to activate the MfR correlated to potency to stimulate male sex determination of offspring (pyriproxyfen>methyl farnesoate>methoprene, kinoprene). Daphnids were exposed to concentrations of pyriproxyfen and physiologic responses determined over multiple generations. Survivial, growth, and sex of maternal organisms were not affected by pyriproxyfen exposure. Sex ratio among offspring (generation 2) were increasingly skewed in favor of males with increasing pyriproxyfen concentration; while, the number of offspring per brood was progressively reduced. Female generation 2 daphnids were reared to reproductive maturity in the absence of pyriproxyfen. Sex ratios of offspring (generation 3) were not affected in this pyriproxyfen lineage, however, the number of offspring per brood, again, was significantly reduced. Conclusions Results reveal likely components to a hormone/receptor signaling pathway in a crustacean that orchestrates transgenerational modifications to important population metrics (sex ratios, fecundity of females). A model is provided that describes how these signaling processes can facilitate population sustainability under normal conditions or threaten sustainability when perturbed by environmental chemicals.}, number={4}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={LeBlanc, Gerald A. and Wang, Ying H. and Holmes, Charisse N. and Kwon, Gwijun and Medlock, Elizabeth K.}, editor={He, BinEditor}, year={2013}, month={Apr}, pages={e61715} }