Molecular design of hypothalamus development
| Autor: | Maria Eleni Kastriti, Roman A. Romanov, Frédéric Clotman, Matthias Farlik, Katsuhiko Nishimori, Francois Lallemend, John G. Parnavelas, Tibor Harkany, Solomiia Korchynska, Erik Keimpema, Patrick Rebernik, Maja Zupancic, Igor Adameyko, Martin Häring, Christoph Bock, Konstantin Popadin, Tomas Hökfelt, Evgenii O. Tretiakov, Marco Benevento, William Andrews |
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| Přispěvatelé: | UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cellular differentiation Dopamine Gene regulatory network Hypothalamus Neuropeptide Glutamic Acid Nerve Tissue Proteins Biology Regulon Article 03 medical and health sciences Mice 0302 clinical medicine Ectoderm medicine Morphogenesis Animals Cell Lineage Gene Regulatory Networks GABAergic Neurons Receptors Immunologic Transcription factor gamma-Aminobutyric Acid 030304 developmental biology Regulation of gene expression 0303 health sciences Neurotransmitter Agents Multidisciplinary Dopaminergic Neurons Neuropeptides Glutamate receptor Gene Expression Regulation Developmental Cell Differentiation nervous system Female Neuroscience Neuroglia 030217 neurology & neurosurgery medicine.drug Genome-Wide Association Study Signal Transduction Transcription Factors |
| Zdroj: | Nature Nature, Vol. 582, no. 7811, p. 246-252 (2020) |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | A wealth of specialized neuroendocrine command systems intercalated within the hypothalamus control the most fundamental physiological needs in vertebrates1,2. Nevertheless, we lack a developmental blueprint that integrates the molecular determinants of neuronal and glial diversity along temporal and spatial scales of hypothalamus development3. Here we combine single-cell RNA sequencing of 51,199 mouse cells of ectodermal origin, gene regulatory network (GRN) screens in conjunction with genome-wide association study-based disease phenotyping, and genetic lineage reconstruction to show that nine glial and thirty-three neuronal subtypes are generated by mid-gestation under the control of distinct GRNs. Combinatorial molecular codes that arise from neurotransmitters, neuropeptides and transcription factors are minimally required to decode the taxonomical hierarchy of hypothalamic neurons. The differentiation of γ-aminobutyric acid (GABA) and dopamine neurons, but not glutamate neurons, relies on quasi-stable intermediate states, with a pool of GABA progenitors giving rise to dopamine cells4. We found an unexpected abundance of chemotropic proliferation and guidance cues that are commonly implicated in dorsal (cortical) patterning5 in the hypothalamus. In particular, loss of SLIT-ROBO signalling impaired both the production and positioning of periventricular dopamine neurons. Overall, we identify molecular principles that shape the developmental architecture of the hypothalamus and show how neuronal heterogeneity is transformed into a multimodal neural unit to provide virtually infinite adaptive potential throughout life. |
| Databáze: | OpenAIRE |
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