Academic literature on the topic 'Granule Neuron Progenitors'

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Journal articles on the topic "Granule Neuron Progenitors"

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Poudel, Phanindra Prasad, Chacchu Bhattarai, Arnab Ghosh, and Sneha Guruprasad Kalthur. "Expression of ATOH1 gene and activated signaling pathways for the neurogenesis of cerebellar granule cells: A review." Neuroscience Research Notes 5, no. 2 (April 28, 2022): 125. http://dx.doi.org/10.31117/neuroscirn.v5i2.125.

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Granule cells in the cerebellum are derived by the proliferation of cells from the rhombic lips of the metencephalon. Atonal homolog 1 (ATOH1), a protein encoding proneural gene, plays an essential role in the neurogenesis of the cerebellar granule cells. It encodes the basic helix loop helix (bHLH) family of transcription factor ATOH1. Expression of the ATOH1 gene in the rhombic lips of the metencephalon results in specification and proliferation of the granule neuron progenitors. Four major signaling pathways- Sonic hedgehog (Shh), Notch, Wingless related integration site (Wnt) and Bone morphogenetic protein (BMP) play an essential role in the regulation of the ATOH1 gene. Shh, Notch and Wnt signalings induce expression of the ATOH1 gene for the proliferation of the granule neuron progenitors whereas BMP signaling is involved in the differentiation of the granule neuron progenitors into the granule cells. Aberrant expression and mutation of the ATOH1 gene result in cerebellar medulloblastoma, the phenotype of trembling gait, cerebellar ataxia and hearing loss.
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Gao, W. Q., and M. E. Hatten. "Immortalizing oncogenes subvert the establishment of granule cell identity in developing cerebellum." Development 120, no. 5 (May 1, 1994): 1059–70. http://dx.doi.org/10.1242/dev.120.5.1059.

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After implantation into the external germinal layer of early postnatal cerebellum, primary external germinal layer progenitor cells gave rise exclusively to granule neurons. In contrast, all major classes of cerebellar cells were observed following implantation of embryonic day 13 cerebellar precursor cells into the external germinal layer. These results suggest that granule cells arise from precursors with a restricted potential. In contrast to results with the primary external germinal layer population, cell lines established from external germinal layer cells, by infection with a retrovirus containing the SV40 large T-antigen oncogene, gave rise to several cerebellar cell types upon implantation. These included granule neurons, one subclass of stellate interneurons, Golgi cells, Bergmann glia and astrocytes. From these results, we conclude that early postnatal external germinal layer progenitors are normally fated to a granule cell identity and that expression of the SV40 large T-antigen oncogene subverts mechanisms that control granule neuron fate.
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Aiello, Giuseppe, and Luca Tiberi. "TMOD-05. IN VIVO REPROGRAMMING OF POSTMITOTIC NEURONS INDUCES MEDULLOBLASTOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi263. http://dx.doi.org/10.1093/neuonc/noz175.1104.

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Abstract It is widely accepted that the “cell of origin” of tumors has to possess a proliferative capacity. Particularly for brain cancer, the transition of neural progenitors to differentiated postmitotic neurons is considered irreversible in physiological and pathological conditions. Therefore, postmitotic neurons have not been considered as suitable cell-of-origin for brain cancer. Here, we show that neurons reprograming may occur upon Shh activation and it leads to medulloblastoma (MB) formation in vivo. Shh MB is a cerebellar tumor, found in infants and adults that is thought to originate from cerebellar granule neuron progenitors. More recently, it was discovered that the two different forms of SHH MB are distinguished by different transcriptome/methylome levels suggesting that the adult SHH MB may originate from a different cell-of-origin. Relying on these data, we take advantage of a conditional Cre-Lox recombination system to recapitulate the human adult medulloblastoma pathogenesis in mice and demonstrate that post-migratory mature granule neurons can be reprogrammed in vivo. Furthermore, to define the contribution of chromatin changes in granule neurons dedifferentiation in response to Shh activation, we profiled changes in chromatin accessibility by ATAC-seq both in mouse tissue samples and also in human neurons. Upon Shh pathway activation we detected the presence of hyper-accessible chromatin regions corresponding to cis-regulatory elements specifically favouring activation of enhancers and super-enhancers. Our novel model of cancer development could explain the human SHH medulloblastoma onset in adult individuals where granule neuron progenitors are no more present. We strongly believe that our model represents an important starting point to study other tissues where postmitotic cells might originate cancer and therefore open a new field in cancer and stem cell biology.
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Mayerl, Steffen, Andrea Alcaide Martin, Reinhard Bauer, Markus Schwaninger, Heike Heuer, and Charles ffrench-Constant. "Distinct Actions of the Thyroid Hormone Transporters Mct8 and Oatp1c1 in Murine Adult Hippocampal Neurogenesis." Cells 11, no. 3 (February 2, 2022): 524. http://dx.doi.org/10.3390/cells11030524.

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Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) result in Allan-Herndon-Dudley Syndrome, a severe form of psychomotor retardation, while inactivating mutations in another TH transporter, organic anion transporting polypeptide 1c1 (OATP1C1), are linked to juvenile neurodegeneration. These diseases point to essential roles for TH transporters in CNS function. We recently defined the presence of Mct8 in adult hippocampal progenitors and mature granule cell neurons and unraveled cell-autonomous and indirect requirements for Mct8 in adult hippocampal neurogenesis. Here, we investigated whether Oatp1c1 is involved in the hippocampal neurogenic process in concert with Mct8. We detected Oatp1c1 gene expression activity and transcripts in subsets of progenitors, neurons and niche cells in the dentate gyrus. Absence of Oatp1c1 resulted in increased neuroblast and reduced immature neuron numbers in 6-month-old Oatp1c1ko and Mct8/Oatp1c1 double knockout (M/Odko) mice. Reduced EdU-label retention in Mct8ko and M/Odko mice confirmed the impact of Mct8 on neuron formation. In contrast, no significant effect of Oatp1c1 loss on granule cell neuron production and anxiety-like behavior in the open field arena were seen. Together, our results reinforce that distinct actions of each TH transporter are required at multiple stages to ensure proper adult hippocampal neurogenesis.
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Cui, Hong, and Robert F. Bulleit. "Potassium chloride inhibits proliferation of cerebellar granule neuron progenitors." Developmental Brain Research 106, no. 1-2 (March 1998): 129–35. http://dx.doi.org/10.1016/s0165-3806(97)00204-6.

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Yang, X. W., R. Zhong, and N. Heintz. "Granule cell specification in the developing mouse brain as defined by expression of the zinc finger transcription factor RU49." Development 122, no. 2 (February 1, 1996): 555–66. http://dx.doi.org/10.1242/dev.122.2.555.

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The creation of specific neuronal cell types within the developing brain is a critical and unsolved biological problem. Precedent from invertebrate development, and from vertebrate myogenesis and lymphogenesis, has established that cell specification often involves transcription factors that are expressed throughout the differentiation of a given cell type. In this study, we have identified in Zn2+ finger transcription factor RU49 as a definitive marker for the cerebellar granule neuron lineage. Thus, RU49 is expressed in the earliest granule cell progenitors at the rhombic lip as they separate from the ventricular zone of the neural tube to generate a secondary proliferative matrix, and it continues to be expressed in differentiating and mature granule neurons. Proliferating granule cell progenitors isolated from the rhombic lip at E14 or from the external germinal layer at P6 continue to express RU49 in vitro. Both the olfactory bulb and dentate gyrus granule cell lineages also express this factor as they are generated with the developing brain. RU49 binds a novel bipartite DNA-binding element in a manner consistent with chemical rules governing the DNA-binding specificity of this class of transcription factor. The novel biochemical properties of RU49 and its restricted expression within the three lineages of CNS granule neurons suggest that RU49 may play a critical role in their specification. Furthermore, these results raise the interesting possibility that the generation of these three neuronal populations to form displaced germinative zones within the developing brain may reflect their use of a common developmental mechanism involving RU49.
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Haldipur, P., I. Sivaprakasam, V. Periasamy, S. Govindan, and S. Mani. "Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum." Biology Open 4, no. 7 (May 15, 2015): 865–72. http://dx.doi.org/10.1242/bio.009886.

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Mani, Shyamala, Saranya Radhakrishnan, Rajit Narayanan Cheramangalam, Shalini Harkar, Samyutha Rajendran, and Narendrakumar Ramanan. "Shh-Mediated Increase in β-Catenin Levels Maintains Cerebellar Granule Neuron Progenitors in Proliferation." Cerebellum 19, no. 5 (June 3, 2020): 645–64. http://dx.doi.org/10.1007/s12311-020-01138-2.

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Chatterjee, Anindo, Kaviya Chinnappa, Narendrakumar Ramanan, and Shyamala Mani. "Centrosome Inheritance Does Not Regulate Cell Fate in Granule Neuron Progenitors of the Developing Cerebellum." Cerebellum 17, no. 5 (April 16, 2018): 685–91. http://dx.doi.org/10.1007/s12311-018-0935-4.

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Ha, Seungshin, Prem P. Tripathi, Ray A. Daza, Robert F. Hevner, and David R. Beier. "Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis." Journal of Developmental Biology 8, no. 3 (September 18, 2020): 20. http://dx.doi.org/10.3390/jdb8030020.

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We have previously described hypomorphic reelin (Reln) mutant mice, RelnCTRdel, in which the morphology of the dentate gyrus is distinct from that seen in reeler mice. In the RelnCTRdel mutant, the infrapyramidal blade of the dentate gyrus fails to extend, while the suprapyramidal blade forms with a relatively compact granule neuron layer. Underlying this defect, we now report several developmental anomalies in the RelnCTRdel dentate gyrus. Most strikingly, the distribution of Cajal-Retzius cells was aberrant; Cajal-Retzius neurons were increased in the suprapyramidal blade, but were greatly reduced along the subpial surface of the prospective infrapyramidal blade. We also observed multiple abnormalities of the fimbriodentate junction. Firstly, progenitor cells were distributed abnormally; the “neurogenic cluster” at the fimbriodentate junction was absent, lacking the normal accumulation of Tbr2-positive intermediate progenitors. However, the number of dividing cells in the dentate gyrus was not generally decreased. Secondly, a defect of secondary glial scaffold formation, limited to the infrapyramidal blade, was observed. The densely radiating glial fibers characteristic of the normal fimbriodentate junction were absent in mutants. These fibers might be required for migration of progenitors, which may account for the failure of neurogenic cluster formation. These findings suggest the importance of the secondary scaffold and neurogenic cluster of the fimbriodentate junction in morphogenesis of the mammalian dentate gyrus. Our study provides direct genetic evidence showing that normal RELN function is required for Cajal-Retzius cell positioning in the dentate gyrus, and for formation of the fimbriodentate junction to promote infrapyramidal blade extension.
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Dissertations / Theses on the topic "Granule Neuron Progenitors"

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Weeranantanapan, Oratai. "The role of L1-CNTNs in controlling SHH-induced proliferation of cerebellar granule neuron progenitors." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/6180/.

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Bou-Rouphaël, Johnny. "A new role for Barhl1 in a cerebellar germinative zone as inhibitor of T-cell factors transcriptional activity." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS009.

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Le cervelet humain contient plus de 50 % des neurones cérébraux. Les neurones granulaires cérébelleux représentent la population neuronale majeure. Les progéniteurs des neurones granulaires (GNP), définis par l’expression de Atoh1, émergent à partir de la lèvre rhombique supérieure (URL), une zone germinative située dans le territoire cérébelleux. Au cours du développement, les GNP prolifèrent, migrent et se différencient. Chacun de ces processus est régulé par un certain nombre de facteurs de transcription et de voies de signalisation. Les « T-Cell Factors » (Tcf/Lef) » sont des effecteurs transcriptionnels agissant en aval de la signalisation Wnt/β-caténine. Bien que les Tcf soient transcriptionnellement actifs dans la URL, leur(s) fonction(s) et leur(s) régulateur(s) développementaux n'ont été étudié. Le facteur de transcription « BarH-like 1 » (Barhl1) est exprimé dans les GNPs engagés, situés dans des zones dépourvues d'une activité transcriptionnelle Tcf. Par conséquent, les objectifs de cette thèse étaient d'étudier les fonctions de Tcf et Barhl1 en tant que régulateurs du développement des GNPs chez le Xénope. Les données présentées dans cette thèse englobent une analyse approfondie des marqueurs majeurs impliqués dans le développement des GNPs chez les amphibiens, et une étude des fonctions de Barhl1 et Tcf dans ce processus développemental. Nos expériences de gain et de perte de fonction, ainsi que l'analyse transcriptomique en absence de Barhl1 dans le rhombomère 1 valident un rôle clé de Tcf en tant qu'activateur transcriptionnel de atoh1 et en tant qu'inducteur du territoire cérébelleux, et un rôle pour Barhl1 en tant qu'inhibiteur développemental de l’activité Tcf, permettant aux GNPs de sortir de l'URL. Nous avons identifié des gènes cibles clés inhibés par Barhl1, et impliqués dans le maintien d’une zone germinative
The human cerebellum hosts more than 50% of all brain neurons. Cerebellar granule neurons are the smallest and most abundant neurons. atonal homologue 1 (Atoh1)-expressing granule neuron progenitors (GNPs) emerge from the upper rhombic lip (URL), a germinative zone located in the cerebellar primordium and displaying features of a niche of neural stem cells. GNPs proliferate, migrate, and differentiate to settle into the internal granule layer. These processes are tightly regulated by a number of transcription factors and signaling pathways. T-Cell Factor/Lymphoid Enhancer-binding Factor (Tcf/Lef) are transcriptional effectors acting downstream of Wnt/β-catenin signaling. Although Tcf is transcriptionally active in the URL, neither its function(s) nor its developmental regulator(s) have been addressed in this area. The transcription factor BarH-like 1 (Barhl1) is expressed in committed GNPs located in areas devoid of Tcf transcriptional activity. The aims of this thesis were to investigate the functions of Tcf and of Barhl1 as regulators of GNPs development using amphibian as experimental model. The data presented in this work encompass a thorough analysis of the spatial and temporal expressions of key markers involved in GNP development in amphibian, and an investigation of Barhl1 and Tcf functions in this developmental process. Our gain and loss of function experiments, together with the transcriptomic analysis of Barhl1 depletion in the rhombomere 1 validate a key role for Tcf as a transcriptional activator of atoh1 and as an inducer of the URL territory, and for Barhl1 as a developmental inhibitor of Tcf activity allowing GNPs to exit the URL. We identified key genes inhibited by Barhl1 and involved in the maintenance of URL germinative zone
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Goodwin, Laura Rose. "The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38201.

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Recent studies have uncovered de novo mutations of the gene encoding the chromatin remodelling protein Snf2l in patients with schizophrenia, Rett-like syndrome and intellectual disability. Snf2l and its closely related protein, Snf2h, play a critical role in embryonic and post-natal brain development. Murine models lacking functional Snf2h or Snf2l point to complementary activities of these remodelers; Snf2h cKO mice present with a significantly reduced cerebellum, while Snf2l Ex6DEL (exon 6 deleted) cerebella are larger than their wild-type counterparts. Granule neuron progenitors (GNPs) isolated from Ex6DEL cerebella display delayed cell cycle exit and hindered terminal differentiation compared to wild-type controls. Moreover, loss of Snf2l activity results in widespread transcriptome shifts which underlie the Ex6DEL GNP differentiation phenotype. In particular, key transcription factors are differentially expressed without Snf2l remodelling activity. We confirm that ERK pathway activation is misregulated in Ex6DEL GNPs, possibly in response to elevated fibroblast growth factor 8 (Fgf8) expression in these cultures. We find that Snf2l activity maintains the chromatin landscape throughout GNP differentiation, as Ex6DEL cultures have a global increase in chromatin accessibility. We suggest that Snf2l-mediated chromatin condensation is responsible for proper regulation of gene expression programs in GNP differentiation.
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Chang, Chia-Hsiang, and 張家祥. "Atoh1 requires primary cilia for the expansion of granule neuron progenitors by modulating centriolar satellites." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/ww438x.

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博士
國立陽明大學
分子醫學博士學位學程
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In this thesis, we showed that how the cerebellar granular progenitor cells (GNPs) sensitize the Sonic hedgehog signaling (SHH) during cerebellar development. Importantly, by using the in vivo cerebellar electroporation and granular neuron purification, we found that the basic helix-loop-helix transcription factor, Atoh1, maintains the ciliated states of GNPs. As Atoh1 is required for the GNP neurogenesis, we identified that this activity is mediated through its regulation on the centriolar satellites, a multiple protein complex required for ciliogenesis. Next, we showed that Atoh1 is able to regulate the length of primary cilium in different cell lines.This property is possibly mediated through its transcriptional target, Gli2. Finally, we identified how Gli2 utilized the autophagy-dependent Ofd1 removal for the regulation on the ciliary length.
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Wortham, Matthew. "The Role of Otx2 in Bypassing Restrictions of Hindbrain Progenitor Cell Proliferation and the Mechanisms of its Dysregulation in Medulloblastoma." Diss., 2012. http://hdl.handle.net/10161/6158.

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Medulloblastoma is the most common malignant brain tumor in children. The understanding of the genetic alterations in this tumor is emergent, and many such genetic driver events have yet to be functionally-characterized. Our studies have sought to understand the causes and consequences of OTX2 dysregulation in established medulloblastomas and in its putative cellular origins. Using a tumor genetic approach, we have uncovered frequent OTX2 copy number gains driving expression of this oncogene in a subset of medulloblastomas. However, OTX2 is frequently expressed in medulloblastomas independent of genomic copy number gain, and we thus sought to understand the transcriptional regulation of this gene in these tumors. We have found that chromatin accessibility, promoter DNA methylation, and activity of a distal downstream enhancer is distinct between OTX2-expressing and -nonexpressing medulloblastomas. Notably, autoregulation serves to maintain OTX2 expression in some medulloblastomas, whereas DNA methylation actively suppresses OTX2 in tumors not expressing this gene. Finally, we describe the effect of expressing Otx2 (the mouse homolog of OTX2) aberrantly in the developing mouse hindbrain, revealing that Otx2 disrupts spatiotemporal restrictions of neuronal progenitor cell proliferation. The effect of Otx2 in vivo is transient, with ectopically-proliferating cells give way to differentiated neurons. We found that OTX2 expression was not able to give rise to high penetrance medulloblastoma when combined with P53 deletion or double heterozygosity for P53 and PTEN. Thus, although Otx2 alters migration and proliferation dynamics of hindbrain neuronal progenitor cells, further studies are needed to identify the genetic alterations that cooperate with this oncogene to give rise to medulloblastoma.


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"High Resolution Identification of Bioparticle Subpopulations with Electrophysical Properties." Doctoral diss., 2020. http://hdl.handle.net/2286/R.I.57025.

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abstract: There is increasing interest and demand in biology studies for identifying and characterizing rare cells or bioparticle subtypes. These subpopulations demonstrate special function, as examples, in multipotent proliferation, immune system response, and cancer diagnosis. Current techniques for separation and identification of these targets lack the accuracy and sensitivity needed to interrogate the complex and diverse bioparticle mixtures. High resolution separations of unlabeled and unaltered cells is an emerging capability. In particular, electric field-driven punctuated microgradient separations have shown high resolution separations of bioparticles. These separations are based on biophysical properties of the un-altered bioparticles. Here, the properties of the bioparticles were identified by ratio of electrokinetic (EK) to dielectrophoretic (DEP) mobilities. As part of this dissertation, high-resolution separations have been applied to neural stem and progenitor cells (NSPCs). The abundance of NSPCs captured with different range of ratio of EK to DEP mobilities are consistent with the final fate trends of the populations. This supports the idea of unbiased and unlabeled high-resolution separation of NSPCs to specific fates is possible. In addition, a new strategy to generate reproducible subpopulations using varied applied potential were employed for studying insulin vesicles from beta cells. The isolated subpopulations demonstrated that the insulin vesicles are heterogenous and showed different distribution of mobility ratios when compared with glucose treated insulin vesicles. This is consistent with existing vesicle density and local concentration data. Furthermore, proteins, which are accepted as challenging small bioparticles to be captured by electrophysical method, were concentrated by this technique. Proteins including IgG, lysozyme, alpha-chymotrypsinogen A were differentiated and characterized with the ratio factor. An extremely narrow bandwidth and high resolution characterization technique, which is experimentally simple and fast, has been developed for proteins. Finally, the native whole cell separation technique has also been applied for Salmonella serotype identification and differentiation for the first time. The technique generated full differentiation of four serotypes of Salmonella. These works may lead to a less expensive and more decentralized new tool and method for transplantation, proteomics, basic research, and microbiologists, working in parallel with other characterization methods.
Dissertation/Thesis
Doctoral Dissertation Chemistry 2020
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Book chapters on the topic "Granule Neuron Progenitors"

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Ocasio, Jennifer Karin. "Maintaining Cerebellar Granule Neuron Progenitors in Cell Culture." In Methods in Molecular Biology, 9–12. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2752-5_2.

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Nanjangud, Gouri. "Conventional and Spectral Karyotyping of Murine Cerebellar Granule Neuron Progenitors." In Methods in Molecular Biology, 25–45. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2752-5_4.

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Ocasio, Jennifer Karin. "Dissociation of Cerebellar Granule Neuron Progenitors for Culture, FACS, Transcriptomics, and Molecular Biology." In Methods in Molecular Biology, 3–7. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2752-5_1.

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Ocasio, Jennifer Karin. "Proliferation Analysis of Cerebellar Granule Neuron Progenitors for Microcephaly Research, Using Immunofluorescent Staining and Flow Cytometry." In Methods in Molecular Biology, 13–23. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2752-5_3.

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