Abstract
Tanycytes, a specialized type of ependymoglial cell, modulate an interesting cycle of communication between the brain and the periphery for energy homeostasis and reproduction. While most circulating factors do not enter the brain because of the blood–brain barrier (BBB), homeostatic signals from the periphery converge on the hypothalamus—a brain region influencing feeding and energy expenditure—through a privileged route that bypasses the brain barrier. Research on the why’s and the wherefore’s of this peculiar brain–periphery communication has made substantial progress in the recent past. One of the compelling revelations has been the ability of tanycytes to adapt their physiology based on the metabolic status of an individual—a key to understanding how tanycytes regulate the transfer of peripheral metabolic hormones into the brain and communicate reciprocally with brain neuronal networks for the regulation of food intake and energy homeostasis. It has been shown that tanycytes adapt by altering the functional and structural organization of the blood–hypothalamus barrier under different metabolic conditions. Moreover, attempts have been made to decode the plasticity and the diversity of tanycytes by morphological and transcriptomic analyses, primarily at the single-cell level. Tanycytes also possess neural stem cell properties as a result of their putative descent from radial glial cells, and may promote hypothalamic neurogenesis in response to dietary or reproductive signals. Thus, tanycytes form the gatekeepers of metabolic signals connecting the loop of behavior, hormonal changes, signal transduction, and neuronal activation. In this chapter, we assess recent advances in the understanding of tanycytic plasticity and function in the hypothalamus and the associated molecular mechanisms, with special emphasis on the techniques and experimental models implemented to achieve these objectives.
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References
Anand Kumar TC, Knowles F (1967) A system linking the third ventricle with the pars tuberalis of the rhesus monkey [14]. Nature 215:54–55. https://doi.org/10.1038/215054a0.
Balland E et al (2014) Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab 19(2):293–301. https://doi.org/10.1016/j.cmet.2013.12.015.
Bolborea M et al (2020) Hypothalamic tanycytes generate acute hyperphagia through activation of the arcuate neuronal network. Proc Natl Acad Sci USA 117(25):14473–14481. https://doi.org/10.1073/pnas.1919887117
Campbell JN et al (2017) A molecular census of arcuate hypothalamus and median eminence cell types. Nat Neurosci 20(3):484–496. https://doi.org/10.1038/nn.4495.
Caro JF et al (1996) Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348(9021):159–161. https://doi.org/10.1016/S0140-6736(96)03173-X
Chachlaki K, Prevot V (2020) Nitric oxide signalling in the brain and its control of bodily functions. Br J Pharmacol 177(24):5437–5458. https://doi.org/10.1111/bph.14800
Chefer VI et al (2009) Overview of brain microdialysis. Curr Protoc Neurosci. p. Unit7.1. https://doi.org/10.1002/0471142301.ns0701s47
Chen R et al (2017) Single-cell RNA-Seq reveals hypothalamic cell diversity. Cell Reports 18(13):3227–3241. https://doi.org/10.1016/j.celrep.2017.03.004
Chmielewski A et al (2019) Preclinical assessment of leptin transport into the cerebrospinal fluid in diet-induced obese minipigs. Obesity (Silver Spring, MD) 27(6):950–956. https://doi.org/10.1002/oby.22465
Conductier G et al (2013) Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume. Nat Neurosci 16(7):845–847. https://doi.org/10.1038/nn.3401
Farkas E et al (2020) A glial-neuronal circuit in the median eminence regulates thyrotropin-releasing hormone-release via the endocannabinoid system. iScience 23(3):100921. https://doi.org/10.1016/j.isci.2020.100921
Faouzi M et al (2007) Differential accessibility of circulating leptin to individual hypothalamic sites. Endocrinology 148(11):5414–5423. https://doi.org/10.1210/en.2007-0655
Feil S, Valtcheva N, Feil R (2009) Inducible cre mice. Methods Mol Biol 530:343–363. https://doi.org/10.1007/978-1-59745-471-1_18.
Fekete C, Lechan RM (2014) Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr Rev 35(2):159–194. https://doi.org/10.1210/er.2013-1087
Frayling C, Britton R, Dale N (2011) ATP-mediated glucosensing by hypothalamic tanycytes. J Physiol 589(9):2275–2286. https://doi.org/10.1113/jphysiol.2010.202051
Gabery S et al (2020) Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insights 5(6):e133429. https://doi.org/10.1172/jci.insight.133429
Geller S et al (2019) Tanycytes regulate lipid homeostasis by sensing free fatty acids and signaling to key hypothalamic neuronal populations via FGF21 secretion. Cell Metab. 30(4):833–844.e7. https://doi.org/10.1016/j.cmet.2019.08.004
Goodman T, Hajihosseini MK (2015) Hypothalamic tanycytes-masters and servants of metabolic, neuroendocrine, and neurogenic functions. Front Neurosci 9:387. https://doi.org/10.3389/fnins.2015.00387
Haan N et al (2013) Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus. J Neurosci 33(14):6170–6180. https://doi.org/10.1523/JNEUROSCI.2437-12.2013
Habib N et al (2016) Div-Seq: single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons. Science 353(6302):925–928. https://doi.org/10.1126/science.aad7038.
Habib N et al (2017) Massively parallel single-nucleus RNA-seq with DroNc-seq. Nat Methods 14(10):955–958. https://doi.org/10.1038/nmeth.4407.
Hagemann-Jensen M et al (2018) Small-seq for single-cell small-RNA sequencing. Nat Protoc 13(10):2407–2424. https://doi.org/10.1038/s41596-018-0049-y.
Harrison L et al (2019) Fluorescent blood-brain barrier tracing shows intact leptin transport in obese mice. Int J Obes (2005) 43(6):1305–1318. https://doi.org/10.1038/s41366-018-0221-z.
Horstmann E (1954) The fiber glia of selacean brain. Z Zellforsch Mikrosk Anat 39(6):588–617
Jikumaru M et al (2007) Effect of starvation on the survival of male and female mice. Physiol Chem Phys Med NMR 39(2):247–257
Kano M et al (2019) Tanycyte-like cells derived from mouse embryonic stem culture show hypothalamic neural stem/progenitor cell functions. Endocrinology 160(7):1701–1718. https://doi.org/10.1210/en.2019-00105
Kleinert M et al (2018) Time-resolved hypothalamic open flow micro-perfusion reveals normal leptin transport across the blood–brain barrier in leptin resistant mice. Mol Metab 13:77–82. https://doi.org/10.1016/j.molmet.2018.04.008
Langlet F et al (2013) Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab 17(4):607–617. https://doi.org/10.1016/j.cmet.2013.03.004
Lazutkaite G et al (2017) Amino acid sensing in hypothalamic tanycytes via umami taste receptors. Mol Metab 6(11):1480–1492. https://doi.org/10.1016/j.molmet.2017.08.015
Lee DA et al (2012) Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nat Neurosci 15(5):700–702. https://doi.org/10.1038/nn.3079
Leeners B et al (2017) Ovarian hormones and obesity. Hum Reprod Update 23(3):300–321. https://doi.org/10.1093/humupd/dmw045
Liu Z et al (2018) Short-term tamoxifen treatment has long-term effects on metabolism in high-fat diet-fed mice with involvement of Nmnat2 in POMC neurons. FEBS Lett 592(19):3305–3316. https://doi.org/10.1002/1873-3468.13240
Meister B et al (1988) DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein in tanycytes of the mediobasal hypothalamus: distribution and relation to dopamine and luteinizing hormone-releasing hormone neurons and other glial elements. Neuroscience 27(2):607–622. https://doi.org/10.1016/0306-4522(88)90292-8
Mirzadeh Z et al (2017) Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories. Nat Commun 8:13759. https://doi.org/10.1038/ncomms13759.
Müller-Fielitz H, Schwaninger M (2019) The role of tanycytes in the hypothalamus-pituitary-thyroid axis and the possibilities for their genetic manipulation. Exp Clin Endocrinol Diabetes. https://doi.org/10.1055/a-1065-1855
Pak T et al (2014) ‘Rax-CreERT2 knock-in mice: a tool for selective and conditional gene deletion in progenitor cells and radial glia of the retina and hypothalamus. PLoS One
Peitz M et al (2002) Ability of the hydrophobic FGF and basic TAT peptides to promote cellular uptake of recombinant Cre recombinase: a tool for efficient genetic engineering of mammalian genomes. Proc Natl Acad Sci 99(7):4489–4494. https://doi.org/10.1073/pnas.032068699
Pellegrino G et al (2018) A comparative study of the neural stem cell niche in the adult hypothalamus of human, mouse, rat and gray mouse lemur (Microcebus murinus). J Comp Neurol 526(9):1419–1443. https://doi.org/10.1002/cne.24376
Pérez-Martín M et al (2010) IGF-I stimulates neurogenesis in the hypothalamus of adult rats. Eur J Neurosci 31(9):1533–1548. https://doi.org/10.1111/j.1460-9568.2010.07220.x
Prevot V et al (2003) Activation of erbB-1 signaling in tanycytes of the median eminence stimulates transforming growth factor β1 release via prostaglandin E2 production and induces cell plasticity. J Neurosci 23(33):10622–10632. https://doi.org/10.1523/jneurosci.23-33-10622.2003
Prevot V et al (2018) The versatile tanycyte: a hypothalamic integrator of reproduction and energy metabolism. Endocr Rev 39(3):333–368. https://doi.org/10.1210/er.2017-00235
Recabal A et al (2018) Connexin-43 gap junctions are responsible for the hypothalamic tanycyte-coupled network. Front Cell Neurosci 12:406. https://doi.org/10.3389/fncel.2018.00406
Robins SC et al (2013) α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun 4. https://doi.org/10.1038/ncomms3049
Rodríguez EM et al (2005) Hypothalamic tanycytes: a key component of brain-endocrine interaction. Int Rev Cytol 247. https://doi.org/10.1016/S0074-7696(05)47003-5
Schwartz MW et al (1996) Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med 2(5):589–593. https://doi.org/10.1038/nm0596-589
Slezak M et al (2007) Transgenic mice for conditional gene manipulation in astroglial cells. Glia 55(15):1565–1576. https://doi.org/10.1002/glia.20570
Di Spiezio A et al (2018) The LepR-mediated leptin transport across brain barriers controls food reward. Mol Metab 8:13–22. https://doi.org/10.1016/j.molmet.2017.12.001
Szilvásy-Szabó A et al (2017) Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice. Brain Res 1673:64–71. https://doi.org/10.1016/j.brainres.2017.08.010
Wang N et al (2019) Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation. Nat Commun 10(1):1–12. https://doi.org/10.1038/s41467-018-07981-6.
Xu Y et al (2005) Neurogenesis in the ependymal layer of the adult rat 3rd ventricle. Exp Neurol 192(2):251–264. https://doi.org/10.1016/j.expneurol.2004.12.021
Yoo S et al (2019) ‘Tanycyte-independent control of hypothalamic leptin signaling. Front Neurosci 13. https://doi.org/10.3389/fnins.2019.00240
Zhou Y et al (2019) Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance. Nat Commun 10(1):1522. https://doi.org/10.1038/s41467-019-09320-9.
Acknowledgments
This work was supported by the Agence National de la Recherche (ANR, France) Grant ANR-15-CE14-0025, the LabEx EGID, the Fondation pour la Recherche Médicale (FRM, to MD), and the European Research Council (ERC) Synergy Grant WATCH n° 810331.
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Nampoothiri, S., Duquenne, M., Prevot, V. (2021). Unveiling the Importance of Tanycytes in the Control of the Dialogue Between the Brain and the Periphery. In: Tasker, J.G., Bains, J.S., Chowen, J.A. (eds) Glial-Neuronal Signaling in Neuroendocrine Systems. Masterclass in Neuroendocrinology, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-030-62383-8_11
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