Periodic Reporting for period 4 - Secret-Cells (Cellular diversity and stress-induced cell-state switches in the mammalian hypothalamus)
Reporting period: 2021-03-01 to 2021-08-31
Molecular interrogation of hypothalamic organization: (Romanov et al., Nat Neurosci. (2017))
Molecular diversity of corticotropin-releasing factor-containing neurons: (Romanov et al., J Endocrinol (2017))
A novel output pathway of CRH neurons uses volume transmission to orchestrate post-traumatic cortical sensitization: (Alpar et al., EMBOJ (2018))
Hypothalamic long-distance signals by neuropeptides: (Alpar et al., Current Open Neurobiol (2019))
Adverse effects of maternal high-fat diets on brain development: (Cinquina et al., Mol Psychiatry (2020))
Developmental organization of the hypothalamus: (Romanov et al., Nature (2020))
Neurohormonal hypothalamic circuit for paternal behaviour: (Stagkourakis et al., Cell (2020))
Identification of ALK in thinness: (Orthofer et al., Cell (2020))
Life-long impairment of glucose homeostasis by prenatal prychostimulant exposure: (Korchynska et al., EMBOJ (2020))
functional heterogeneity of POMC neurones in the arcuate nucleus: (Saucisse et al., Cell Rep (2021))
Results Related to Theme 2:
Secretagogin regulates neuroblast migration by regulating matrix metalloprotease release: (Hanics et al., PNAS (2017))
Secretagogin regulates beta-cell turnover: (Malenczyk et al., EMBOJ (2017))
Secretagogin controls beta-cell specification by configuring permissive transcirption factor landscape: (Malenczyk et al., Mol Metab (2018))
Calcium-binding protein NECAB2 facilitates pain: (Zhang et al. J Clin Invest (2018))
Psychostimulant sensitivity of hypothalamic and limbic neurone identify by Patch-seq (Fuzik et al., PNAS (2019))
Secretagogin involvement in NMDA receptor turnover (Hevesi et al., PNAS, 2021)).
Conclusions
Overall, through our published studies we have made significant advances in not only understanding the molecular and cellular organization of the mammalian hypothalamus but also, by developing novel technologies, linking molecular determinants of select neuroendocrine command neurons to the context-dependent release of hypothalamic hormones.
i) generation of a cellular atlas of the hypothalamus (Romanov et al., Nature 2020, Romanov et al., Nat Neurosci (2017); Romanov et al., J Endocrinol (2017); Romanov et al. Ann Rev Neurosci (2019)),
ii) description of a novel multimodal signaling system that links stress neurons to norepinephrine centers of the brain for cortical activaton upon stress (Alpar et al., EMBOJ (2018)), and the analysis and recognition of ventricular ependymal heterogeneity (Alpar et al., Curr Opin Neurobiol (2018)),
iii) molecular dissection of secretagogin function in the brain (related to neuronal migration and replacement; Hanics et al., PNAS (2017)), spinal cord/pain perception (Zhang et al. J Clin Invest (2018)) and pancreas (for the control of beta cell turnover; Malenczyk et al., EMBOJ (2017) and particularly with Pdx1 transcription factors; Malenczyk et al., Mol Metab (2018)),
iv) In the process of these studies, we have actively collaborated on brain (dopamine cells; Rivetti di val Chervo et al., Nat Biotech (2017), hypothalamic neurons: Saucisse et al., Cell Rep (2021), Stagkourakis et al., Cell (2020), Orthofer et al., Cell (2020)), pain (Peng et al., Science (2017)), diabetes (Li et al., Cell (2017)) and lung development (Cohen et al., Cell (2018)),
v) Moreover, my mentoring of an up-and-coming new generation of researchers led to spin-off on taste perception (Romanov et al., Sci Signal (2018)) and on the role of GPR55, one of the previously less characterized G protein-coupled receptors (GPCRs), in gating salivation (Korchynska et al., JCI Insight (2019)), a novel neuron type in the mammalian indusium griseum (Fuzik et al., PNAS (2019)) and the effect of maternal diet choices on fetal brain development (Cinquina et al., Mol Psychiatry (202).
vi) We have generated mouse lines that have been published (CCK-DsRed/GAD67-GFP: Calvigioni et al., Cereb Cortex (2017); secretagogin null and tissue-specific knockout: Malenczyk et al., EMBOJ (2018); secretagogin-Cre: Alpar et al., EMBOJ (2018)) and made available to the scientific community free-of-charge.