Hedgehog signaling is necessary and sufficient to mediate craniofacial plasticity in teleosts.

Phenotypic plasticity, the ability of a single genotype to produce multiple phenotypes under different environmental conditions, is critical for the origins and maintenance of biodiversity; however, the genetic mechanisms underlying plasticity as well as how variation in those mechanisms can drive evolutionary change remain poorly understood. Here, we examine the cichlid feeding apparatus, an icon of both prodigious evolutionary divergence and adaptive phenotypic plasticity. We first provide a tissue-level mechanism for plasticity in craniofacial shape by measuring rates of bone deposition within functionally salient elements of the feeding apparatus in fishes forced to employ alternate foraging modes. We show that levels and patterns of phenotypic plasticity are distinct among closely related cichlid species, underscoring the evolutionary potential of this trait. Next, we demonstrate that hedgehog (Hh) signaling, which has been implicated in the evolutionary divergence of cichlid feeding architecture, is associated with environmentally induced rates of bone deposition. Finally, to demonstrate that Hh levels are the cause of the plastic response and not simply the consequence of producing more bone, we use transgenic zebrafish in which Hh levels could be experimentally manipulated under different foraging conditions. Notably, we find that the ability to modulate bone deposition rates in different environments is dampened when Hh levels are reduced, whereas the sensitivity of bone deposition to different mechanical demands increases with elevated Hh levels. These data advance a mechanistic understanding of phenotypic plasticity in the teleost feeding apparatus and in doing so contribute key insights into the origins of adaptive morphological radiations.

Genetic analyses in Lake Malawi cichlids identify new roles for Fgf signaling in scale shape variation.

Elasmoid scales are the most common epithelial appendage among vertebrates, however an understanding of the genetic mechanisms that underlie variation in scale shape is lacking. Using an F2 mapping cross between morphologically distinct cichlid species, we identified >40 QTL for scale shape at different body positions. We show that while certain regions of the genome regulate variation in multiple scales, most are specific to scales at distinct positions. This suggests a degree of regional modularity in scale development. We also identified a single QTL for variation in scale shape disparity across the body. Finally, we screened a QTL hotspot for candidate loci, and identified the Fgf receptor fgfr1b as a prime target. Quantitative rtPCR and small molecule manipulation support a role for Fgf signaling in shaping cichlid scales. While Fgfs have previously been implicated in scale loss, these data reveal new roles for the pathway in scale shape variation.

Simultaneous cytosolic delivery of a chemotherapeutic and siRNA using nanoparticle-stabilized nanocapsules.

We report on nanoparticle-stabilized capsules (NPSCs) as a platform for the co-delivery of survivin-targeted siRNA and tamoxifen. These capsules feature an inner oil core that provides a carrier for tamoxifen, and is coated on the surface with positively charged nanoparticles self-assembled with siRNA. The multifaceted chemical nature of the NPSC system enables the simultaneous delivery of both payloads directly into the cytosol in vitro. The NPSC co-delivery of tamoxifen and survivin-targeted siRNA into breast cancer cells disables the pathways that inhibit apoptosis, resulting in enhanced breast cell death.