Priyanjali Ghosh

Investigating the effects of altered thyroid hormone levels on neural stem cell proliferation in the larval zebrafish hypothalamus. part of CUREnet:CURE Collection
The central nervous system of most vertebrate species consists of zones of neural stem cell (NSC) proliferation which retain the ability to undergo neuro/gliogenesis well into adulthood [1]. The two primary regions of adult neurogenesis in mammals are the ventricular and subventricular zones (V-SVZ) of the lateral ventricles and the subgranular zone (SGZ) of hippocampus [2–7]. Additionally, adult neurogenesis in the mammalian hypothalamus has also been reported [8–11]. Unlike mammals, neurogenesis is more abundant in reptiles, amphibians and fish [3, 12]. In fact, studies have identified 16 different regions of proliferation and neurogenesis in the adult zebrafish brain, and unlike mammalian species, neurogenesis occurs in all of these subdivisions in the zebrafish brain [2, 13, 14]. This makes the zebrafish a fantastic model organism for studying NSC proliferation and neuro/gliogenesis. Recent studies show that there are striking similarities and differences across all vertebrate species in the factors and mechanisms that regulate NSC proliferation and neuro/gliogenesis [1]. Thus, understanding these mechanisms is critical to understanding regenerative neurogenesis and to developing treatments for neurodegenerative diseases. One such interesting factor known to regulate NSC behavior throughout vertebrate life is thyroid hormone (TH). Appropriate amounts of TH are necessary for proper brain development in all vertebrates and studies have shown that TH plays an important role in maintaining NSC proliferation and fate determination in the central nervous system [15]. However, studies performed in rats and mice to understand the effects of TH on NSC proliferation reveal contradictory results. For example, low levels of TH are shown to decrease the proliferative rates of NSC in SVZ of mice [16] whereas the opposite effect is observed in the rat SVZ [17]. Not only does this suggest that the effect of TH may vary between species, it encourages us to explore the role of TH in the zebrafish brain. Specifically, for this CURE course, we are interested in studying the role of TH on NSC proliferation in the zebrafish hypothalamus. Why the hypothalamus? For one, the hypothalamus is the most ancient and evolutionarily conserved part of the vertebrate brain [18]. Second, life-long hypothalamic neurogenesis has been documented in rodents, zebrafish, and likely humans [5, 11, 19]. Lastly, very little is known about the role of TH in regulating the NSC proliferation in the hypothalamus (including that of the zebrafish), making the goal of thus CURE course novel.