In Search of Molecular Markers for Cerebellar Neurons

Abstract

The cerebellum, the region of the brain primarily responsible for motor coordination and balance, also contributes to non-motor functions, such as cognition, speech, and language comprehension. Maldevelopment and dysfunction of the cerebellum lead to cerebellar ataxia and may even be associated with autism, depression, and cognitive deficits. Hence, normal development of the cerebellum and its neuronal circuitry is critical for the cerebellum to function properly. Although nine major types of cerebellar neurons have been identified in the cerebellar cortex to date, the exact functions of each type are not fully understood due to a lack of cell-specific markers in neurons that renders cell-specific labeling and functional study by genetic manipulation unfeasible. The availability of cell-specific markers is thus vital for understanding the role of each neuronal type in the cerebellum and for elucidating the interactions between cell types within both the developing and mature cerebellum. This review discusses various technical approaches and recent progress in the search for cell-specific markers for cerebellar neurons.

Expression of ATOH1 gene and activated signaling pathways for the neurogenesis of cerebellar granule cells: A review

“…Among different types of neurons in the cerebellum granule cells are the highest in number and have intricate connections with other neurons for the functional integrity of the cerebellum. It is essential to understand the neurogenesis of the cerebellar granule cells which are playing an essential role in maintaining the fine movement of the body (Tam et al, 2021).…”

“…In vivo and in vitro studies in mouse, zebrafish, and human samples Amore et al, 2021*;Belzunce et al, 2020;Chang et al, 2019;Diaz et al, 2002;Englund et al, 2006;Fink et al, 2006;Hoshino et al, 2005;Klisch et al, 2011;Leto et al, 2016*;Machold & Fishell., 2005;Marzban et al, 2015*;Miyashita et al, 2021;NCBI., 2021;Puelles & Ferran, 2012*;Rahimi-Balaei et al, 2018*;Sheykholeslami et al, 2013 ;Tam et al, 2021*;Wang et al, 2005;Wefers et al, 2018;Wingate, 2005*;Xie et al, 2017;Yamada et al, 2014…”

“…Two germinative zones, the ventricular zone and rhombic lips, are established in the cerebellar primordium. Granule cells and other glutamatergic neurons are derived by the proliferation of cells from the rhombic lips whereas purkinje cells and other gamma aminobutyric acidergic (GABAergic) neurons are derived by the proliferation of cells from the ventricular zone of the metencephalon (Rahimi-Balaei et al, 2018;Tam et al, 2021). Histological studies showed that the external granular layer is the outermost layer of the fetal cerebellum and it is formed by the migration of cells from the rhombic lips (Amore et al, 2021).…”

Incorporation of 5-Bromo-2′-deoxyuridine into DNA and Proliferative Behavior of Cerebellar Neuroblasts: All That Glitters Is Not Gold

“…In adults, the cerebellar cortex shows a regular trilaminate architecture comprising a ganglionar layer sandwiched between an outer molecular layer and an inner granular layer. The neuronal component of these layers is integrated in a nucleocortical network [41,42], and presents distinctive dendritic arborizations, axons, and perikaryal as well as molecular markers [43][44][45][46]. This regular cytoarchitecture has allowed us to ascertain the successive phases in the ontogeny of the cerebellum, and to analyze the cellular and molecular mechanisms involved in its development [39,47].…”

Molecular Mechanisms of Neural Circuit Development and Regeneration

“…In this Special Issue, the roles of Tau [ 2 ], heme oxygenase [ 3 ], and calsequestrin [ 4 ] in axonal regeneration, circuit formation, and synaptic plasticity are revisited. Tam et al also report on their search for cerebellar markers that may propel research into the (mal)development and (dys)function of the cerebellum [ 5 ]. Furthermore, novel research on the molecular and electrophysiological mechanisms by which GABAergic input regulates adult neurogenesis in the dentate gyrus is presented [ 6 ], as well as on the role of developmentally regulated GTP-binding protein 2 (DRG2) as a modulator of the dopaminergic system [ 7 ].…”