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Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development
Human cerebellar development is fundamentally linked to its function. Here, the authors combine single-cell transcriptomics, spatial transcriptomics, and single-cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development.
- Suijuan Zhong
- , Mengdi Wang
- & Qian Wu
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Article
| Open Access
Thalamocortical control of cell-type specificity drives circuits for processing whisker-related information in mouse barrel cortex
Excitatory spiny stellate neurons in the somatosensory cortex are shaped by innervating thalamic inputs and unique expression of genes. Here, the authors show that these neurons play a crucial role in processing distinct whisker signals and forming specialized circuits for sensory perception.
- Timothy R. Young
- , Mariko Yamamoto
- & Tomomi Shimogori
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| Open Access
Erythropoietin re-wires cognition-associated transcriptional networks
The mechanism and physiological role of brain-expressed Erythropoietin (EPO) is unclear. Here, authors show that the trajectory of pyramidal neurons is maneuvered by EPO, befitting the neurogenic hypothesis of alleviating mood, memory, and cognition.
- Manvendra Singh
- , Ying Zhao
- & Hannelore Ehrenreich
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| Open Access
St18 specifies globus pallidus projection neuron identity in MGE lineage
The medial ganglionic eminence produces both interneurons and projection neurons, though how this fate choice is made is not well established. Here they show that St18 regulates migration and morphology of MGE neurons, inducing projection neuron fates.
- Luke F. Nunnelly
- , Melissa Campbell
- & Edmund Au
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Article
| Open Access
Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex
During development, astrocytes are generated from radial glia, and migrate to the cortical plate, but the process of astrocyte migration during development is not fully understood. Here the authors labelled cells derived from the cortical ventricular zone in the late stages of cortical plate development in mice, and identified a migration mode in which cells move rapidly and almost at random within the intermediate zone and the cortical plate.
- Hidenori Tabata
- , Megumi Sasaki
- & Kazunori Nakajima
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| Open Access
Maintenance of neurotransmitter identity by Hox proteins through a homeostatic mechanism
To remain functional throughout life, neuronal cells must maintain the ability to synthesize and release specific neurotransmitters. Here, the authors show that this ability critically depends on the activity of Hox proteins.
- Weidong Feng
- , Honorine Destain
- & Paschalis Kratsios
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Article
| Open Access
MTG8 interacts with LHX6 to specify cortical interneuron subtype identity
There is a large diversity of inhibitory interneurons in the mammalian cerebral cortex. How this emerges during embryogenesis remains unclear. Here, the authors identify MTG8 as a co-factor of LHX6 and a new regulator of cortical interneuron development.
- Zeinab Asgarian
- , Marcio Guiomar Oliveira
- & Nicoletta Kessaris
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| Open Access
Single-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification
This study chronicles dynamic gene expression in differentiating spiral ganglion neurons from murine embryonic day 14.5 to postnatal stage, establishes their lineage trajectories, and identifies molecular determinants of cell fate decision.
- Charles Petitpré
- , Louis Faure
- & Francois Lallemend
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| Open Access
A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing
During development, neural progenitors generate a variety of neural types sequentially. Here the authors examine gene expression patterns in Drosophila neural progenitors at single-cell level, and identify a gene regulatory network controlling the sequential generation of different neural types.
- Hailun Zhu
- , Sihai Dave Zhao
- & Xin Li
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| Open Access
Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module
Adult neural stem cells are derived from an embryonic population of slowcycling progenitor cells, though how reduced cycling speed leads to establishment of the adult population has remained elusive. Here they show that non-oscillatory Notch-Hey signaling induced by slow-cycling contributes to long term maintenance of neural stem cells.
- Yujin Harada
- , Mayumi Yamada
- & Yukiko Gotoh
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Article
| Open Access
Coordination of two enhancers drives expression of olfactory trace amine-associated receptors
In our nose, some neuron subpopulations express a family of trace amine associated receptors (TAARs, smelling e.g., rotten fish). Fei et al. identify two conserved enhancers across placental mammals named TAAR enhancer 1 and 2 that coordinately regulate expression of the entire Taar gene repertoire.
- Aimei Fei
- , Wanqing Wu
- & Qian Li
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Article
| Open Access
The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development
The cellular and molecular mechanisms regulating hypothalamic patterning and differentiation are unclear. Here, the authors profiled the transcriptome of the developing hypothalamus at single cell level, providing a resource to hypothalamic development in health and disease.
- Dong Won Kim
- , Parris Whitney Washington
- & Seth Blackshaw
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| Open Access
Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates
The diversity of primary sensory neurons and how fate choice is determined is unclear. Here, the authors use single cell RNA sequencing analysis of early murine somatosensory neurons to show that sensory neuron diversity is achieved by a transition through a bi-potential intermediate state.
- Louis Faure
- , Yiqiao Wang
- & Saida Hadjab
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| Open Access
Dscam1 establishes the columnar units through lineage-dependent repulsion between sister neurons in the fly brain
Columns are the functional and morphological unit of the brain, but how neurons assemble into this structure was unclear. Here, the authors show that Dscam gene rewires neurons that derive from the same stem cell to establish columns through the process of lineage-dependent repulsion.
- Chuyan Liu
- , Olena Trush
- & Makoto Sato
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| Open Access
Nolz1 expression is required in dopaminergic axon guidance and striatal innervation
The mechanisms regulating midbrain dopaminergic innervation during development are unclear. Here, the authors showed that Nolz1 is required for axonal guidance of dopaminergic neurons during embryonic development of the mouse brain.
- Clement Soleilhavoup
- , Marco Travaglio
- & Lia Panman
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| Open Access
Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons
Although cortical GABAergic interneuron (CIN) dysfunction is implicated in several neuropsychiatric disorders, we still know very little about how they attain their unique properties or how their dysfunction impacts neuropsychiatric disorders. In this study, authors show that conditional loss of Tsc1, causes SST+ CINs, which are distinct from PV+ CINs, to express PV and adopt fast-spiking properties, via MTOR activity
- Ruchi Malik
- , Emily Ling-Lin Pai
- & Daniel Vogt
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| Open Access
Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity
It is traditionally believed that callosal and non-callosal fates are determined early after a neuron’s birth, and that cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel cortex project only ipsilaterally. However, here authors demonstrate, using a novel axonal retrotracing strategy, that L4 neurons develop transient interhemispheric axons that are refined in an area- and layer-specific manner during postnatal development.
- N. S. De León Reyes
- , S. Mederos
- & M. Nieto
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| Open Access
Precisely controlling endogenous protein dosage in hPSCs and derivatives to model FOXG1 syndrome
Altered dosage of developmental regulators such as transcription factors can result in disorders, such as FOXG1 syndrome. Here, the authors demonstrate the utility of SMASh technology for modulating protein dosage by modeling FOXG1 syndrome using human pluripotent stem cell-derived neurons and neural organoids.
- Wenliang Zhu
- , Boya Zhang
- & Baoyang Hu
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| Open Access
Sensory neuron lineage mapping and manipulation in the Drosophila olfactory system
Few tools exist to study molecular diversity during neurodevelopment. Here the authors apply a genetic immortalization method in Drosophila to generate a fate map of olfactory sensory lineages, examine the relationships of this map and the neuroanatomical, molecular and evolutionary properties of the mature circuits, and identify a novel factor controlling lineage development.
- Phing Chian Chai
- , Steeve Cruchet
- & Richard Benton
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| Open Access
Progressive divisions of multipotent neural progenitors generate late-born chandelier cells in the neocortex
Diverse GABAergic neurons arise from progenitors in the medial ganglionic eminence. Here, the authors show these progenitors are progressively fate-restricted, with early-born interneurons occupying cortex in an “inside-out” pattern and later-born types like chandelier cells generated “outside-in”.
- Khadeejah T. Sultan
- , Wenying Angela Liu
- & Song-Hai Shi
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| Open Access
Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons
In the hypothalamus, the arcuate nucleus (ARC) contains AgRP-neurons that regulate energy balance as well as GHRH-neurons that regulate linear growth. Here, the authors looked at how the transcription factors Dlx1/2 and Otp link development of AgRP- and GHRH-neurons.
- Bora Lee
- , Janghyun Kim
- & Jae W. Lee
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| Open Access
Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories
Ependymal cells lining the adult brain ventricles are comprised of multiciliated cells and a rare subpopulation with two cilia (E2 cells) whose origin and function remain unknown. Here the authors find E2 cells in the 3rd ventricle of mice and humans, along with a third ependymal cell type with only a primary cilium, and provide details of their marker profile and developmental origins.
- Zaman Mirzadeh
- , Yael Kusne
- & Arturo Alvarez-Buylla
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| Open Access
Tectal-derived interneurons contribute to phasic and tonic inhibition in the visual thalamus
The development and function of thalamic interneurons is only partially understood. Here the authors describe the unexpected mesencephalic origin of the GABAergic interneurons of the visual thalamus that provide both phasic and tonic modulation of thalamic relay neuron excitability.
- Polona Jager
- , Zhiwen Ye
- & Alessio Delogu
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Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate
Differentiation of embryonic stem cells (ESCs) into neural lineages involves epigenetic changes. Here the authors show that transient histone deacetylation promotes the transition from epiblast stem cells to neural progenitors during mouse ESC differentiation and show that this effect is partly mediated by the restriction of Nodal signalling by histone deacetylase 1.
- Pingyu Liu
- , Xiaoyang Dou
- & Naihe Jing
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Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system
Proteins known as fate determinants trigger specific transcriptional programs that drive the progression from multipotent precursors towards specific cellular identities. Here the authors study the regulation of the glial determinant, Gcm, and its role in the lineage specification of neural precursors in Drosophila.
- Hakima Flici
- , Pierre B. Cattenoz
- & Angela Giangrande
iPSC-derived models of PACS1 syndrome reveal transcriptional and functional deficits in neuron activity