Neurogenesis in the cerebellum

Chizhikov, Victor V.; Millen, Kathleen J.

doi:10.1016/b978-0-12-814405-3.00016-3

Cited by 5 publications

(12 citation statements)

References 178 publications

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“…Normal granule cell development is critical for building an appropriately sized functional cerebellum (Sillitoe and Joyner, 2007; Basson and Wingate, 2013; Chizhikov and Millen, 2013). Thus, after observing a reduced number of granule cell precursors in preterm pigs, we sought to determine the mechanisms underlying this phenotype.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to general cell-cycle regulatory molecules, many tissue specific proteins regulate development of granule cells, including transcription factors Atoh1, Pax6, Zic1, Zic4 and signaling molecules Shh and Jag1, which act upstream of or interact with general regulators of the cell cycle (Chizhikov and Millen, 2013; Leto et al, 2016). Using qRT-PCR, we found that expression of Atoh1 , which positively regulates proliferation of granule cell precursors (Flora et al, 2009), was reduced in the EGL of preterm pigs relative to both naturally born term controls and those delivered via c-section (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…During development, cerebellar neurons originate from two germinal zones that arise in early embryonic cerebellar anlage: the cerebellar ventricular zone, which gives rise to GABAergic neurons, such as Purkinje cells and molecular layer interneurons, and the rhombic lip, which gives rise to glutamatergic cerebellar neurons, such as granule cells (Chizhikov and Millen, 2013). Upon exiting the ventricular zone, Purkinje cells migrate radially toward the cerebellar surface forming a multilayered Purkinje cell layer, which later resolves into a Purkinje cell monolayer.…”

Section: Introductionmentioning

confidence: 99%

“…In the aforementioned study, however, gene expression was analyzed using total cerebellar RNA. Since development of different cerebellar populations is controlled by different genetic programs (Chizhikov and Millen, 2013; Basson and Wingate, 2013; Sillitoe and Joyner 2007; Goldowitz and Hamre, 1998), it is likely that preterm birth modulates expression of genes in a cell-type specific manner. Thus, gene expression differences in preterm subjects may be hard to detect by analyzing total cerebellar RNA, highlighting the need to analyze individual cerebellar cell types.…”

Section: Introductionmentioning

confidence: 99%

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Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia

Iskusnykh

Buddington

Chizhikov

2018

Experimental Neurology

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Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants. In this study, we analyzed the cerebellum of preterm pigs delivered via c-section at 91% term and raised for 10 days, until term-equivalent age. The pigs did not receive any treatments known or suspected to affect cerebellar development and had no evidence of brain damage. Term pigs sacrificed at birth were used as controls. Immunohistochemical analysis revealed that preterm birth did not affect either size or numbers of Purkinje cells or molecular layer interneurons at term-equivalent age. The number of granule cell precursors and Bergmann glial fibers, however, were reduced in preterm pigs. Preterm pigs had reduced proliferation but not differentiation of granule cells. qRT-PCR analysis of laser capture microdissected external granule cell layer showed that preterm pigs had a reduced expression of Ccnd1 (Cyclin D1), Ccnb1 (Cyclin B1), granule cell master regulatory transcription factor Atoh1, and signaling molecule Jag1. In vitro rescue experiments identified Jag1 as a central granule cell gene affected by preterm birth. Thus, preterm birth and precocious exposure to the ex-utero environment disrupt cerebellum by modulating expression of key cerebellar developmental genes, predominantly affecting development of granule precursors and Bergmann glia.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia

Iskusnykh

Buddington

Chizhikov

2018

Experimental Neurology

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“…Human cerebellar neurogenesis occurs over a prolonged period, beginning in the first trimester of pregnancy and continuing after birth [6][7][8]. The fetal cerebellum arises in the anterior hindbrain and harbors two germinal zones that contain proliferating progenitors: the rhombic lip, which generates glutamatergic granule neurons (granule cells) and the ventricular zone, which generates Purkinje neurons and the molecular layer interneurons and glia [6,9,10]. During embryonic development, proliferating granule precursors exit the rhombic lip and migrate towards the cerebellar pial surface, forming the external granule cell layer (EGL) [11,12].…”

Section: Introductionmentioning

confidence: 99%

Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs

2020

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Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic acid (DHA) esterified to phosphatidylserine (PS) had cerebellar weights similar to those of newborn term pigs and were heavier than control preterm pigs. However, whether PS-DHA promotes the development of specific cerebellar cell populations or enhances key developmental processes remains unknown. Here we investigated the effects of the PS-DHA on development of the cerebellum in preterm pigs delivered via caesarean section and reared for ten days on a milk replacer with either PS-DHA (experimental group) or sunflower oil (control group). Upon necropsy, key cerebellar populations were analyzed using immunohistochemistry. Consumption of PS-DHA was associated with the expansion of undifferentiated granule cell precursors and increased proliferation in the external granule cell layer (EGL). Preterm pigs that received PS-DHA also had significantly fewer apoptotic cells in the internal granule cell layer (IGL) that contains differentiated granule neurons. PS-DHA did not affect the number of differentiating granule cells in the inner EGL, thickness of the inner EGL, density of Purkinje cells, or Bergmann glial fibers, or diameter of Purkinje cells. Thus, PS-DHA may support cerebellar development in preterm subjects by enhancing proliferation of granule cells, a process specifically inhibited by preterm birth, and increasing the survival of granule cells in the IGL. These findings suggest that PS-DHA is a promising candidate for clinical studies directed at enhancing brain development.

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Roof Plate in Cerebellar Neurogenesis

Chizhikov

2021

Handbook of the Cerebellum and Cerebellar Disorders

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The roof plate is a distinct group of cells located at the dorsal midline of the developing central nervous system that extends along its entire anterior-posterior axis. In the developing hindbrain, most of the roof plate broadens into a simple epithelial layer covering the dorsal opening of the 4th ventricle. As development proceeds, the 4th ventricle roof plate differentiates into the choroid plexus epithelium, which produces cerebrospinal fluid and serves as a bloodcerebrospinal fluid barrier. A growing amount of evidence indicates that both

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Neurogenesis in the cerebellum

Cited by 5 publications

References 178 publications

Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia

Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia

Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs

Roof Plate in Cerebellar Neurogenesis

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