Consensus Paper: Cerebellar Development

Abstract

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

Genome integrity and disease prevention in the nervous system

“…Deletion of ATR in cortical progenitors results in a reduced cortical size, although with the six-layer lamination (that reflects functional compartmentation in the cortex) still present, suggesting a generalized cellular attrition (Lee et al 2012c). In contrast, deletion of ATR in the developing cerebellum has little apparent effect until embryonic day 16, a stage when granule neuron progenitor numbers rapidly increase via sonic hedgehog-driven proliferation from the rhombic lip (Hatten and Heintz 1995;Leto et al 2016). At this point in cerebellar development, ATR-null granule neuron expansion ceases, and cerebellar development is stalled (Lee et al 2012c).…”

Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells

“…The generation of cerebellar neurons from human iPSCs aims to recapitulate the complex in vivo molecular events that direct the specification of cerebellar neurons, and circuit formation during human embryogenesis [15][16][17] . Early protocols attempted cerebellar differentiation using either mouse or human embryonic stem cells (ESCs) [18][19][20][21] .…”

“…Interestingly, mounting evidence from cell and animal models indicates that abnormal Purkinje cell development, including impaired dendritic arborisation, spine development and synaptogenesis, and related functional changes, may contribute to the pathogenesis of ataxias, including neurodegenerative ataxias 15 . Thus, it will be extremely interesting to investigate whether iPSC-derived human cerebellar neurons display any developmental abnormalities.…”

“…Ishida et al recently reported the differentiation of iPSCs into Purkinje cells from SCA6 patients that harbour a polyglutamine expansion in the calcium channel Cav2.1 25 . Patient Purkinje cells were more vulnerable to depletion of thyroid hormone triiodothyronine (T3), an important growth hormone for maturation and maintenance of Purkinje cells, as demonstrated by a decrease in cell number and reduction in dendritic arbours in patient cells compared to controls 15,42 . This study highlights the potential of patient iPSC-derived Purkinje cells to model developmental and diseaserelevant ataxia phenotypes.…”

Effect of maternal exposure of silver nanoparticles on the histogenesis of cerebellum in post-implantation of albino rats embryos

“…The cerebellum is the second largest part of the brain therefore, the cerebellum is an ideal useful model for studying many aspects of neural development, because each stage of development has a distinct morphology and special histological features with different types of cells [3]. The volume of the human cerebellum increases ~10× between 20 and 40 weeks of gestation, with the surface area increasing much more due to the formation of folia and lobules [4], [5].Physiologically, the cerebellum is considered as the key regulator of the central nervous system in the mammals, because it regulates the motor and sensory activities such as attention, balance, languages and some emotional functions like fear and pleasure [6], [7] Because rapid development of nanotechnology has led to the wide application of nanoparticles (NPs) in various fields such as, catalysis and biotechnology including cosmetics, pharmaceutics and medicines [8] However, there is a lack of information concerning the impact of NPs on human health, as it was proved that the nanoparticles could be administered to human body by several routes including inhalation, ingestion, dermal penetration, and injection, followed by the distribution of these nanoparticles to various tissues through systemic circulation [9]. The NP size is important in CNS penetration, with several studies suggesting a 20-70nm diameter as being optimal for transport; Surface charge can also facilitate NP-mediated BBB disruption.…”