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Fitch, R.

Publications and source records attributed to Fitch, R..

2 recordsLinked to original sources

Passive accumulation of alkaloids in putatively non-toxic frogs challenges paradigms of the origins of acquired chemical defenses

Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs of the family Dendrobatidae have evolved the novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling for alkaloids has been biased towards colorful species, without similar attention paid to inconspicuous ones that are often assumed to be undefended. As a result, our understanding of how chemical defense evolved in this group is incomplete. Here we provide new data showing that, in contrast to previous studies, species from each undefended poison frog clade have measurable yet low amounts of alkaloids. We confirm that undefended dendrobatids regularly consume mites and ants, which are known sources of alkaloids. Thus, our data suggest that diet is insufficient to explain the defended phenotype. Our data support the existence of a phenotypic intermediate between toxin consumption and sequestration -- passive accumulation -- that differs from sequestration in that it involves no derived forms of transport and storage mechanisms yet results in low levels of toxin accumulation. We discuss the concept of passive accumulation and its potential role in the origin of chemical defenses in poison frogs and other toxin-sequestering organisms. In light of ideas from pharmacokinetics we incorporate new and old data from poison frogs into an evolutionary model that could help explain the origins of acquired chemical defenses in animals and provide insight into the molecular processes that govern the fate of ingested toxins. ResumenComprender los origenes de fenotipos novedosos y complejos es un objetivo central en biologia evolutiva. Las ranas venenosas de la familia Dendrobatidae han desarrollado una novedosa habilidad para adquirir alcaloides de su dieta como defensas quimicas, al menos tres veces. Sin embargo, el muestreo de taxones en busca de alcaloides ha estado sesgado hacia las especies coloridas, sin prestar atencion similar a las poco conspicuas que a menudo se presume, no tienen defensas. Como resultado, nuestra comprension de como evolucionan las defensas quimicas en este grupo es incompleta. Aqui, proporcionamos nuevos datos que muestran que, en contraste con estudios anteriores, las especies de cada clado de ranas venenosas no defendidas tienen cantidades bajas pero cuantificables de alcaloides. Confirmamos que los dendrobatidos no defendidos consumen regularmente acaros y hormigas, que son fuentes conocidas de alcaloides. Por lo tanto, nuestros datos sugieren que la dieta es insuficiente para explicar el fenotipo defendido. Nuestros datos respaldan la existencia de un fenotipo intermedio entre consumo y secuestro de toxinas (acumulacion pasiva), que difiere del secuestro en que no implica formas derivadas de mecanismos de transporte y almacenamiento, pero da lugar a bajos niveles de acumulacion de toxinas. Discutimos el concepto de acumulacion pasiva y su potencial rol en el origen de defensas quimicas en ranas venenosas y otros organismos que secuestran toxinas. Considerando ideas de farmacocinetica, incorporamos datos nuevos y antiguos de ranas venenosas dentro de un modelo evolutivo que podria ayudar a explicar los origenes de defensas quimicas adquiridas en animales, y proporcionar una vision de los procesos moleculares que regulan el destino de las toxinas ingeridas.

evolutionary biology↗

Iterative remodeling of the mouse uterus requires Hedgehog signaling

The adult uterus regenerates in the human during the menstrual cycle, and remodels in the mouse during the estrous cycle. Decades of work has demonstrated that this process is controlled by cycling steroid hormones, estrogen and progesterone. However, downstream signaling pathways that link hormonal action to this regeneration and remodeling are yet to be identified in the cycling uterus. We set out to identify these pathways, with the overarching hypothesis that developmental signaling pathways are redeployed in the adult uterus to control remodeling in the mouse. We were surprised to find that the majority of Hedgehog signaling components were transcriptionally co-regulated throughout the estrous cycle. To test the role of Hh signaling in cyclical uterine remodeling, we conditionally knocked out the major activator of the pathway, smoothened (Smo) using the progesterone receptor cre (PR-Cre). In the absence of Hh signaling, the uterus no longer remodels throughout the estrous cycle. We also show that the smooth muscle fibers of the uterus are significantly larger in the conditional knockouts compared to the controls suggesting hypertrophy of the smooth muscle. Our findings support the possibility that this smooth muscle homeostasis may underlie important aspects of uterine function such as contractility during late-stage pregnancy or the development of uterine smooth muscle tumors.

developmental biology↗