scholarly journals Vertebrate brain regeneration – a community effort of fate-restricted precursor cell types

2020 ◽  
Vol 64 ◽  
pp. 101-108
Author(s):  
Christian Lange ◽  
Michael Brand
2021 ◽  
Author(s):  
Shachar Sherman ◽  
Koichi Kawakami ◽  
Herwig Baier

The brain is assembled during development by both innate and experience-dependent mechanisms1-7, but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components7-9. Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs10 and central neurons11-16. Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog17 and gene expression atlas18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz (atoh7-) mutants, in which RGCs do not form19. Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.


2019 ◽  
Author(s):  
Bushra Raj ◽  
Jeffrey A. Farrell ◽  
Aaron McKenna ◽  
Jessica L. Leslie ◽  
Alexander F. Schier

ABSTRACTNeurogenesis in the vertebrate brain comprises many steps ranging from the proliferation of progenitors to the differentiation and maturation of neurons. Although these processes are highly regulated, the landscape of transcriptional changes and progenitor identities underlying brain development are poorly characterized. Here, we describe the first developmental single-cell RNA-seq catalog of more than 200,000 zebrafish brain cells encompassing 12 stages from 12 hours post-fertilization to 15 days post-fertilization. We characterize known and novel gene markers for more than 800 clusters across these timepoints. Our results capture the temporal dynamics of multiple neurogenic waves from embryo to larva that expand neuronal diversity from ∼20 cell types at 12 hpf to ∼100 cell types at 15 dpf. We find that most embryonic neural progenitor states are transient and transcriptionally distinct from long-lasting neural progenitors of post-embryonic stages. Furthermore, we reconstruct cell specification trajectories for the retina and hypothalamus, and identify gene expression cascades and novel markers. Our analysis reveal that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo, while hypothalamic neural progenitors become progressively distinct with developmental time. These data provide the first comprehensive single-cell transcriptomic time course for vertebrate brain development and suggest distinct neurogenic regulatory paradigms between different stages and tissues.


Neuron ◽  
1995 ◽  
Vol 14 (6) ◽  
pp. 1181-1188 ◽  
Author(s):  
Brenda P Williams ◽  
Jack Price

2013 ◽  
Vol 7 ◽  
pp. JEN.S11268 ◽  
Author(s):  
Thierry D. Charlier ◽  
Charlotte A. Cornil ◽  
Jacques Balthazart

Numerous steroid hormones, including 17β-estradiol (E2), activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the key-limiting enzyme in the production of estrogens, and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 concentrations. The mechanisms that might mediate such rapid enzymatic changes are not fully understood but are currently under intense scrutiny. Recent studies in our laboratory indicate that brain aromatase activity is rapidly inhibited by an increase in intracellular calcium concentration resulting from potassium-induced depolarization or from the activation of glutamatergic receptors. Phosphorylating conditions also reduce aromatase activity within minutes, and this inhibition is blocked by the addition of multiple protein kinase inhibitors. This rapid modulation of aromatase activity by phosphorylating conditions is a general mechanism observed in different cell types and tissues derived from a variety of species, including human aromatase expressed in various cell lines. Phosphorylation processes affect aromatase itself and do not involve changes in aromatase protein concentration. The control of aromatase activity by multiple kinases suggests that several amino acids must be concomitantly phosphorylated to modify enzymatic activity but site-directed mutagenesis of several amino acids alone or in combination has not to date revealed the identity of the targeted residue(s). Altogether, the phosphorylation processes affecting aromatase activity provide a new general mechanism by which the concentration of estrogens can be rapidly altered in the brain.


2012 ◽  
Vol 23 (7) ◽  
pp. 742-753 ◽  
Author(s):  
Olivier Bockstael ◽  
Catherine Melas ◽  
Catherine Pythoud ◽  
Marc Levivier ◽  
Douglas McCarty ◽  
...  

2021 ◽  
Author(s):  
Xiaoyu Wei ◽  
Sulei Fu ◽  
Hanbo Li ◽  
Yang Liu ◽  
Shuai Wang ◽  
...  

Brain regeneration requires a precise coordination of complex responses in a time- and region-specific manner. Identifying key cell types and molecules that direct brain regeneration would provide potential targets for the advance of regenerative medicine. However, progress in the field has been hampered largely due to very limited regeneration capacity of the mammalian brain and understanding of the regeneration process at both cellular and molecular level. Here, using axolotl brain with astonishing regeneration ability upon injury, and the Stereo-seq (SpaTial Enhanced REsolution Omics-sequencing), we reconstruct the first architecture of axolotl telencephalon with gene expression profiling at single-cell resolution, and fine cell dynamics maps throughout development and regeneration. Intriguingly, we discover a marked heterogeneity of radial glial cell (RGC) types with distinct behaviors. Of note, one subtype of RGCs is activated since early regeneration stages and proliferates while other RGCs remain dormant. Such RGC subtype appears to be the major cell population involved in early wound healing response and gradually covers the injured area before presumably transformed into the lost neurons. Altogether, our work systematically decodes the complex cellular and molecular dynamics of axolotl telencephalon in development and regeneration, laying the foundation for studying the regulatory mechanism of brain regeneration in future.


2008 ◽  
Vol 205 (5) ◽  
pp. 1187-1199 ◽  
Author(s):  
Claudia Benz ◽  
Vera C. Martins ◽  
Freddy Radtke ◽  
Conrad C. Bleul

T cell development in the thymus depends on continuous colonization by hematopoietic precursors. Several distinct T cell precursors have been identified, but whether one or several independent precursor cell types maintain thymopoiesis is unclear. We have used thymus transplantation and an inducible lineage-tracing system to identify the intrathymic precursor cells among previously described thymus-homing progenitors that give rise to the T cell lineage in the thymus. Extrathymic precursors were not investigated in these studies. Both approaches show that the stream of T cell lineage precursor cells, when entering the thymus, selectively passes through the early T lineage precursor (ETP) stage. Immigrating precursor cells do not exhibit characteristics of double-negative (DN) 1c, DN1d, or DN1e stages, or of populations containing the common lymphoid precursor 2 (CLP-2) or the thymic equivalent of circulating T cell progenitors (CTPs). It remains possible that an unknown hematopoietic precursor cell or previously described extrathymic precursors with a CLP, CLP-2, or CTP phenotype feed into T cell development by circumventing known intrathymic T cell lineage progenitor cells. However, it is clear that of the known intrathymic precursors, only the ETP population contributes significant numbers of T lineage precursors to T cell development.


2021 ◽  
Vol 7 (18) ◽  
pp. eabf7452
Author(s):  
Laurence A. Lemaire ◽  
Chen Cao ◽  
Peter H. Yoon ◽  
Juanjuan Long ◽  
Michael Levine

The hypothalamus coordinates neuroendocrine functions in vertebrates. To explore its evolutionary origin, we describe integrated transcriptome/connectome brain maps for swimming tadpoles of Ciona, which serves as an approximation of the ancestral proto-vertebrate. This map features several cell types related to different regions of the vertebrate hypothalamus, including the mammillary nucleus, the arcuate nucleus, and magnocellular neurons. Coronet cells express melanopsin and share additional properties with the saccus vasculosus, a specialized region of the hypothalamus that mediates photoperiodism in nontropical fishes. Comparative transcriptome analyses identified orthologous cell types for mechanosensory switch neurons, and VP+ and VPR+ relay neurons in different regions of the mouse hypothalamus. These observations provide evidence that the hypothalamus predates the evolution of the vertebrate brain. We discuss the possibility that switch neurons, coronet cells, and FoxP+/VPR+ relay neurons comprise a behavioral circuit that helps trigger metamorphosis of Ciona larvae in response to twilight.


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