Browsing by Author "Zhang, Cindy HaiQin"

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    Rnd2 and Rnd3 expression in the ventromedial hypothalamus is compromised during embryonic development in absence of proneural genes Neurog2 and Ascl1
    (University of Calgary, 2018-09-24) Zhang, Cindy HaiQin; Kurrasch, Deborah M.
    The ventromedial hypothalamus (VMH) is a hypothalamic nucleus with essential roles in homeostatic functions such as satiety signaling and reproductive behaviors. Despite the functional importance of the VMH, mechanisms driving VMH development are just starting to be explored. Among the most important unanswered questions regarding to VMH development is: what are the mechanisms responsible for VMH neurons migrate from their birthplace to their final positions? Here, we investigated whether the absence of the proneural genes Neurogenin-2 (Neurog2) and Achaete-scute homolog 1 (Ascl1) compromises the expression of downstream Rho family GTPase 2 and 3 (Rnd2 and Rnd3), respectively, in migrating VMH neurons. In migrating cortical neurons, Neurog2 has been shown to directly induce Rnd2 expression, and Rnd3 expression is likewise induced by Ascl1. When expressed normally, Rnd2 and Rnd3 both facilitate critical aspects of radial migration, and Rnd3 further maintains the correct timing and direction of migration. We used Ascl1GFP/KI and Neurog2GFP/KI mouse embryos as model organisms. Rnd2 and Rnd3 expression throughout critical development periods was examined by individually immunostaining for anti-Rnd2 and anti-Rnd3 at E12.5, E15.5, and E19.5 slices and imaging slices using compound fluorescence microscopy. VMH neurons expressing Rnd2 and Rnd3 were visually counted and compared with counts of control slices. Up until now, we have found that Ascl1 null embryos had fewer cells expressing Rnd3 at E15.5 and E19.5, and Neurog2 null embryos had fewer cells expressing Rnd2 at E19.5. Preliminary immunostaining results shows a reduction in transcription of both Ascl1 and Neurog 2. Results from this work will shed important insight into the mechanisms employed by hypothalamic neurons during migration. Abnormalities in neuronal migration to the VMH may result in obesity disorders and early puberty; thus, understanding migration mechanisms is an essential first step in developing tools to treat and prevent potentially debilitating conditions.