scholarly journals Early Subset of Cerebellar Nuclei Neurons Derived from Mesencephalon in Mice

2017 ◽  
Author(s):  
Maryam Rahimi-Balaei ◽  
Xiaodan Jiao ◽  
Fiona E. Parkinson ◽  
Behzad Yeganeh ◽  
Hassan Marzban
Keyword(s):  
Neural Crest ◽  
Purkinje Cells ◽  
Ventricular Zone ◽  
Cerebellar Nuclei ◽  
Nerve Fibers ◽  
Neurotrophin Receptor ◽  
Cerebellar Development ◽  
Developing Cerebellum ◽  
Rhombic Lip ◽  
Migratory Pathway

ABSTRACTDuring cerebellar development, cerebellar nuclei (CN) neurons and Purkinje cells are the earliest born among the different neuronal subtypes. Purkinje cells are the sole output of the cerebellar cortex and project to the CN. The CN represents the main output of the cerebellum, which is generated from the rhombic lip and the ventricular zone. We used immunohistochemistry, embryonic cultures, dye tracers and in situ hybridization to examine the origin of a new subset of CN neurons from the mesencephalon during early cerebellar development. Our results show that a subset of CN neurons, which are immunopositive for α-synuclein (SNCA) and Otx2, originate from the mesencephalon and cross the isthmus toward the rostral end of the nuclear transitory zone. Double immunostaining of the SNCA with Otx2 or p75 neurotrophin receptor (p75ntr) indicates that these cells are derived from neural crest cells. We also showed that this population of neurons with nerve fibers terminates at the subpial surface of putative lobules VI/VII. The SNCA+/Otx2+/p75+ cells, which divide the cerebellar primordium into rosterodorsal and caudoventral compartments, show increased cleaved caspase-3 activation, which suggests temporary presence of these cells due to apoptosis. These results strongly suggest that early CN neurons originate from the mesencephalic neural crest population and cross the isthmus to contribute as a subset of the CN. Their temporary presence in the nuclear transitory zone suggests that these neurons/fibers play a regulatory role as a signaling center to attract early afferent pioneer axons and provide neuronal migratory pathway during early cerebellar development.Significance StatementDuring cerebellar development two germinal zones are involved in cerebellar neurogenesis: the rhombic lip and the ventricular zone, which are located in the developing cerebellum itself. Our findings indicate that a subset of cerebellar nuclei neurons have an external origin, the mesencephalon, and they are the earliest born neurons that enter to the developing cerebellum. In this study, we focused on the origin of these cells and traced their migratory pathway from the mesencephalon while crossing the isthmus, followed them when they entered to the developing cerebellum. We also demonstrated their potential role on later born cells during cerebellar development.

scholarly journals Olig3 regulates early cerebellar development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elijah D Lowenstein ◽  
Aleksandra Rusanova ◽  
Jonas Stelzer ◽  
Marc Hernaiz-Llorens ◽  
Adrian E Schroer ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Purkinje Cell ◽  
Ventricular Zone ◽  
Cerebellar Development ◽  
Brain Functions ◽  
Key Factor ◽  
Progenitor Cell Proliferation ◽  
Molecular Machinery ◽  
Neuronal Types ◽  
Rhombic Lip

The mature cerebellum controls motor skill precision and participates in other sophisticated brain functions that include learning, cognition, and speech. Different types of GABAergic and glutamatergic cerebellar neurons originate in temporal order from two progenitor niches, the ventricular zone and rhombic lip, which express the transcription factors Ptf1a and Atoh1, respectively. However, the molecular machinery required to specify the distinct neuronal types emanating from these progenitor zones is still unclear. Here, we uncover the transcription factor Olig3 as a major determinant in generating the earliest neuronal derivatives emanating from both progenitor zones in mice. In the rhombic lip, Olig3 regulates progenitor cell proliferation. In the ventricular zone, Olig3 safeguards Purkinje cell specification by curtailing the expression of Pax2, a transcription factor that suppresses the Purkinje cell differentiation program. Our work thus defines Olig3 as a key factor in early cerebellar development.

scholarly journals Cerebellar nuclei neurons dictate cortical growth through developmental scaling of presynaptic Purkinje cells

2018 ◽  
Author(s):  
Ryan T. Willett ◽  
Alexandre Wojcinski ◽  
N. Sumru Bayin ◽  
Zhimin Lao ◽  
Daniel Stephen ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Granule Cells ◽  
Cell Types ◽  
Cerebellar Nuclei ◽  
Conditional Knockout ◽  
Neural Systems ◽  
Specific Cell ◽  
Embryonic Loss ◽  
Local Circuits ◽  
Rhombic Lip

AbstractEfficient function of neural systems requires the production of specific cell types in the correct proportions. Here we report that reduction of the earliest born neurons of the cerebellum, excitatory cerebellar nuclei neurons (eCN), results in a subsequent reduction in growth of the cerebellar cortex due to an accompanying loss of their presynaptic target Purkinje cells. Conditional knockout of the homeobox genes En1 and En2 (En1/2) in the rhombic lip-derived eCN and granule cell precursors leads to embryonic loss of a subset of medial eCN and cell non-autonomous and location specific loss of Purkinje cells, with subsequent proportional scaling down of cortex growth. We propose that subsets of eCN dictate the survival of their specific Purkinje cell partners, and in turn sonic hedgehog secreted by Purkinje cells scales the expansion of granule cells and interneurons to produce functional local circuits and the proper folded morphology of the cerebellum.

scholarly journals IMMUNOHISTOCHEMICAL STUDY OF CALBINDIN IN THE DEVELOPING CEREBELLUM OF THE RAT

2020 ◽  
Vol 18 (6) ◽  
pp. 692-697
Author(s):  
O. A. Karnyushko ◽  
◽  
S. M. Zimatkin ◽  
Keyword(s):  
Purkinje Cells ◽  
Calcium Binding ◽  
Age Groups ◽  
Physiological Role ◽  
Postnatal Period ◽  
Nerve Fibers ◽  
Adult Rats ◽  
White Rats ◽  
Calbindin D28k ◽  
Developing Cerebellum

Background. Calbindin is a calcium-binding protein that supports calcium homeostasis for the normal functioning of neurons. Purpose. To study the distribution of immunoreactivity of calbindin-D28K in the structures of the developing cerebellum of the rat.Material and methods. The study was performed on 16 outbred white rats of different age groups: 2-, 7-, 15-days (early postnatal period), 45-days (puberty period). The cerebellum samples were taken and fixed in zinc-ethanol-formaldehyde for immunohistochemistry. Calbindin-D28K immunoreactivity was determined on paraffin sections using primary polyclonal rabbit antibodies.Results. In the cerebellar cortex, calbindin immunoreactivity was detected on the 2nd day after development of Purkinje cells (PC) in their perikaryons, and by the 15th day in their dendrites and it did not change by the 45th day. In all terms of the study in PC, it was detected not only in the cytoplasm, but also in their nucleus. In the granular layer, calbindin immunoreactivity decreased in rats in postnatal ontogenesis, however, in adult rats, some neurons were moderately immunopositive. Among them, from the 15th day after birth, the calbindin-immunoreactive afferent nerve fibers running in the white matter were detected. There were no significant differences in the distribution of calbindin between the lobes of the cerebellum of different phylogenetic age. Conclusions. Considering that the expression of сalbindin-D28k is detected throughout the entire period of development of Purkinje cells, as well as its physiological role in maintaining the function and homeostasis of calcium in them, it can be concluded that сalbindin-D28k is a valuable marker for the morphofunctional characteristics of PC in the developing and adult cerebellum of rats in normal and pathological conditions.

scholarly journals Olig3 acts as a master regulator of cerebellar development

2020 ◽  
Author(s):  
Elijah D. Lowenstein ◽  
Aleksandra Rusanova ◽  
Jonas Stelzer ◽  
Marc Hernaiz-Llorens ◽  
Adrian E. Schroer ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ventricular Zone ◽  
Inhibitory Interneuron ◽  
Cerebellar Development ◽  
Brain Functions ◽  
Key Factor ◽  
Progenitor Cell Proliferation ◽  
Molecular Machinery ◽  
Neuronal Types ◽  
Rhombic Lip

AbstractThe mature cerebellum controls motor skill precision and participates in other sophisticated brain functions that include learning, cognition and speech. Different types of GABAergic and glutamatergic cerebellar neurons originate in temporal order from two progenitor niches, the ventricular zone and rhombic lip, which express the transcription factors Ptf1a and Atoh1, respectively. However, the molecular machinery required to specify the distinct neuronal types emanating from these progenitor zones is still unclear. Here, we uncover the transcription factor Olig3 as a major determinant in generating the earliest neuronal derivatives emanating from both progenitor zones. In the rhombic lip, Olig3 regulates progenitor cell proliferation. In the ventricular zone, Olig3 safeguards Purkinje cell specification by curtailing the expression of Pax2, a transcription factor that we found to impose an inhibitory interneuron identity. Our work thus defines Olig3 as a key factor in cerebellar development.

scholarly journals The transcription factor Pou3f1 provides a new map to the glutamatergic neurons of the cerebellar nuclei

2020 ◽  
Author(s):  
Joshua Po Han Wu ◽  
Joanna Yeung ◽  
Sih-Rong Wu ◽  
Huda Zoghbi ◽  
Dan Goldowitz
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Classical Model ◽  
Cerebellar Nuclei ◽  
Glutamatergic Neurons ◽  
Molecular Programming ◽  
Neuron Populations ◽  
Cap Analysis ◽  
Developing Cerebellum ◽  
Rhombic Lip

AbstractPou3f1 is a transcription factor involved in early neural differentiation. Cap Analysis Gene Expression (5’-CAGE) analysis reveals that Pou3f1 transcript is highly enriched in the developing cerebellum. Between embryonic (E) days E10.5 and E12.5, Pou3f1 expression is present prominently along the subpial stream (SS), suggesting that Pou3f1+ cells are glutamatergic cerebellar nuclear (CN) neurons. This finding was confirmed by immunofluorescent (IF) co-labeling of Pou3f1 and Atoh1, the master regulator of cells from the rhombic lip (RL) that are destined for neurons of the glutamatergic lineage, as well as in Atoh1-null tissues, in which Pou3f1 expression is absent. Interestingly, the expression of Pax6, another key molecule for CN neuron survival, does not co-localize with that of Pou3f1. In the Pax6-null Small Eye (Sey) mutant, which is characterized by a loss of many glutamatergic CN neurons, Pou3f1+ CN neurons are still present. Furthermore, Pou3f1-labeled cells do not co-express Tbr1, a well-established marker of glutamatergic CN neurons. These results highlight that Pou3f1+ cells are a distinct and previously unrecognized subtype of glutamatergic CN neurons that do not have the “canonical” sequence of Atoh1→Pax6→Tbr1 expressions. Instead, they express Atoh1, Pou3f1, and other markers of CN neurons, Brn2 and Irx3. These findings illustrate that glutamatergic CN neurons that arise from the RL are composed of molecularly heterogeneous subpopulations that are determined by at least two distinct transcriptional programs.Significance StatementThe present work has identified Pou3f1 as a marker for a previously unidentified subtype of glutamatergic cerebellar nuclear neurons, the principal output neurons of the cerebellum. The classical model of glutamatergic CN neurons development follows the sequential expression of transcription factors Atoh1→Pax6→Tbr1. However, we found that the development of Pou3f1+ neurons requires Atoh1 but not Pax6. Moreover, Pou3f1+ neurons do not express Tbr1, but instead express two other transcription factors, Brn2 and Irx3. Anatomically, Pou3f1+ CN neurons populate the interposed and dentate nuclei, while the Tbr1+ CN neurons populate the fastigial nucleus. These findings reveal the heterogeneity of CN neuron populations and the diversity of molecular programming that lead to different CN neuron subtypes.

A Developmental Study of the Cerebellar Nucleus in the Catshark, a Basal Gnathostome

2017 ◽  
Vol 89 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Sol Pose-Méndez ◽  
Isabel Rodríguez-Moldes ◽  
Eva Candal ◽  
Sylvie Mazan ◽  
Ramón Anadón
Keyword(s):  
Ventricular Zone ◽  
Cerebellar Nuclei ◽  
Cerebellar Nucleus ◽  
Developmental Expression ◽  
Developmental Study ◽  
Evolutionary Innovation ◽  
Evolution And Development ◽  
Rhombic Lip ◽  
Different Sources ◽  
Insight Into

The output of the cerebellar cortex is mainly released via cerebellar nuclei which vary in number and complexity among gnathostomes, extant vertebrates with a cerebellum. Cartilaginous fishes, a basal gnathostome lineage, show a conspicuous, well-organized cerebellar nucleus, unlike ray-finned fishes. To gain insight into the evolution and development of the cerebellar nucleus, we analyzed in the shark Scyliorhinus canicula (a chondrichthyan model species) the developmental expression of several genes coding for transcription factors (ScLhx5,ScLhx9,ScTbr1, and ScEn2) and the distribution of the protein calbindin, since all appear to be involved in cerebellar nuclei patterning in other gnathostomes. Three regions (subventricular, medial or central, and lateral or superficial) became recognizable in the cerebellar nucleus of this shark during development. Present genoarchitectonic and neurochemical data in embryos provide insight into the origin of the cerebellar nucleus in chondrichthyans and support a tripartite mediolateral organization of the cerebellar nucleus, as previously described in adult sharks. Furthermore, the expression pattern of ScLhx5,ScLhx9, and ScTbr1 in this shark, together with that of markers of proliferation, migration, and early differentiation of neurons, is compatible with the hypothesis that, as in mammals, different subsets of cerebellar nucleus neurons are originated from progenitors of 2 different sources: the ventricular zone of the cerebellar plate and the rhombic lip. We also present suggestive evidence that Lhx9 expression is involved in cerebellar nuclei patterning early on in gnathostome evolution, rather than representing an evolutionary innovation of the dentate nucleus in mammals, as previously hypothesized.

scholarly journals SAT-708 The Effect of Soybean Isoflavones in Developing Cerebellum

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Winda Ariyani ◽  
Wataru Miyazaki ◽  
Izuki Amano ◽  
Noriyuki Koibuchi
Keyword(s):  
Mrna Expression ◽  
G Protein ◽  
Purkinje Cells ◽  
Expression Level ◽  
Cerebellar Development ◽  
Mrna Expression Level ◽  
Soybean Isoflavones ◽  
Soybean Isoflavone ◽  
Developing Cerebellum ◽  
G Protein Coupled

Abstract Abstract ENDO 2020 The effect of soybean isoflavones in developing cerebellum Thyroid hormone (TH) receptor (TR) and estrogen receptor (ER) play crucial roles in cerebellar development. TR and ER are involved in Purkinje cells dendrite growth, spines and synapse formation. They also regulate the functional maturation, intracellular metabolism, and migration of neuron and glial. Soybean isoflavones especially genistein, daidzein, and daidzein metabolite, S-equol were known to exert their action through TR, ER, and GPR30, that is a G-protein-coupled ER. However, the mechanisms of soybean isoflavone action on cerebellar development and function have not yet been extensively studied. We evaluated the effects of soybean isoflavone, such as genistein, daidzein, and S-equol, using mouse primary cerebellar culture, astrocyte-enriched culture, and C6 clonal cells. Soybean isoflavone augmented TH- or estradiol (E2)-mediated dendrite arborization of Purkinje cells. Such augmentation was suppressed by G15, a selective G-protein coupled ER (GPR30) antagonist, and ICI 182.780, an antagonist for ERs in both cultures. It also increased mRNA expression level of TH-responsive genes including Mbp, Bdnf, Rc3, Ntf3, Camk2b, and Hr. Moreover, genistein and daidazein also increased mRNA expression level of Syn1, Syp and Psd95 that are involved in synaptic plasticity. On the other hand, in astrocytes, soybean isoflavone activated cell migration and F-actin rearrangements. Such effects were suppressed by G15, but not by ICI 182.780. Knockdown of GPR30 by RNAi also suppressed the cells migration. Protein expression levels of p-Akt (Ser473), p-Rac1/cdc42 (Ser71), RhoA, Rac1/2/3, and cdc42 also increased by soybean isoflavone. Co-exposure with Rhosin HCl, a selective RhoA inhibitor, reduced the cells migration and formation of stress fibers. These findings indicate that sobybean isoflavone may affect cerebellar development by acting to both neurons and astrocytes through several signaling pathways, including TR, ER, and GPR30. Keywords: EDC, ER, TR, GPR30, Neuron, Astrocyte

scholarly journals Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Josef Turecek ◽  
Wade G Regehr
Keyword(s):  
Purkinje Cells ◽  
Inferior Olive ◽  
Release Kinetics ◽  
Vestibular Nuclei ◽  
Cerebellar Nuclei ◽  
Climbing Fiber ◽  
Inhibitory Input ◽  
Deep Cerebellar Nuclei

The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.

Taste buds develop autonomously from endoderm without induction by cephalic neural crest or paraxial mesoderm

Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 949-957 ◽  
Author(s):  
L.A. Barlow ◽  
R.G. Northcutt
Keyword(s):  
Epithelial Cells ◽  
Neural Crest ◽  
Explant Culture ◽  
Nerve Fibers ◽  
Taste Buds ◽  
Paraxial Mesoderm ◽  
Culture Techniques ◽  
Well Differentiated ◽  
Neural Crest Migration

Although it had long been believed that embryonic taste buds in vertebrates were induced to differentiate by ingrowing nerve fibers, we and others have recently shown that embryonic taste buds can develop normally in the complete absence of innervation. This leads to the question of which tissues, if any, induce the formation of taste buds in oropharyngeal endoderm. We proposed that taste buds, like many specialized epithelial cells, might arise via an inductive interaction between the endodermal epithelial cells that line the oropharynx and the adjacent mesenchyme that is derived from both cephalic neural crest and paraxial mesoderm. Using complementary grafting and explant culture techniques, however, we have now found that well-differentiated taste buds will develop in tissue completely devoid of neural crest and paraxial mesoderm derivatives. When the presumptive oropharyngeal region was removed from salamander embryos prior to the onset of cephalic neural crest migration, taste buds developed in grafts and explants coincident with their appearance in intact control embryos. Similarly, explants from neurulae in which movement of paraxial mesoderm had not yet begun also developed taste buds after 9–12 days in vitro. We conclude that neither cranial neural crest nor paraxial mesoderm is responsible for the induction of embryonic taste buds. Surprisingly, the ability to develop taste buds late in embryonic development seems to be an intrinsic feature of the oropharyngeal endoderm that is determined by the completion of gastrulation.

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