19 research outputs found
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Hedgehog Signaling (Hh/Gli) Regulates Neurogenesis in the Zebrafish Hypothalamus
Get PDFThe hypothalamus is the central regulator of a diverse homeostatic processes that are essential for the survival of the animal. Recently, the hypothalamus has been shown to be a neurogenic zone in many animal species including mice, zebrafish, sheep and potentially even humans with hypothalamic neurogenesis implicated in energy metabolism, stress, anxiety and reproduction. However, the identification of the cellular components and the signaling mechanisms regulating hypothalamic neurogenesis are only beginning to be elucidated. My dissertation research elucidates the role of Hh signaling in regulating hypothalamic neurogenesis throughout life. The first chapter of the dissertation offers a survey into the field of neurogenesis with a focus on up-to-date information about hypothalamic neurogenesis. Chapter two demonstrates the role of Hh signaling in the ventral forebrain proliferation. More specifically, we reveal for the first time, that Hh signaling is necessary and sufficient for regulating hypothalamic proliferation rates throughout life. Additionally, we show Hh-responsive radial glia as multipotent neural progenitors giving rise to dopaminergic, GABA-ergic and serotonergic neuronal lineages with Hh signaling being both necessary and sufficient for regulating larval serotonergic cell numbers. Chapter three of my dissertation focuses on a detailed description of the proliferative rates of five progenitor cell types present at the hypothalamic lateral (LR) and posterior (PR) recesses. We show that approximately, 60% of Hh-responsive cells in the PR were PCNA positive compared to approximately 20% of Notch-responsive cells and 10% of Shh-producing cells and no proliferative Wnt-responsive. These analyses reveal striking differences in the proliferative profiles among radial glia in the posterior recess with Hh-responsive cells representing a much more proliferative population that may account for the majority of hypothalamic growth in the larval stages. Lastly, chapter four of the dissertation offers a synthesis of the hypothalamic neurogenesis with a focus on the heterogeneity of the neural progenitor types on this brain region. Taken together, my dissertation work reveals a novel role for Hh signaling as a key molecular regulator of hypothalamic proliferation in the zebrafish hypothalamus and provides a foundation for future studies of a mechanism of action
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Hedgehog signaling is necessary and sufficient to mediate craniofacial plasticity in teleosts
Get PDFPhenotypic 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
