The generation of granule cells during the development and evolution of the cerebellum

Abstract

The cerebellum coordinates vestibular input into the hindbrain to control balance and movement, and its anatomical complexity is increasingly viewed as a high‐throughput processing center for sensory and cognitive functions. Cerebellum development however is relatively simple, and arises from a specialized structure in the anterior hindbrain called the rhombic lip, which along with the ventricular zone of the rostral‐most dorsal hindbrain region, give rise to the distinct cell types that constitute the cerebellum. Granule cells, being the most numerous cell types, arise from the rhombic lip and form a dense and distinct layer of the cerebellar cortex. In this short review, we describe the various strategies used by amniotes and anamniotes to generate and diversify granule cell types during cerebellar development.

The interplay of atoh1 genes in the lower rhombic lip during hindbrain morphogenesis

“…In the URL, atoh1a and atoh1c have equivalent function in the generation of granular cells progenitors [18], whereas we argue that in the LRL atoh1a and atoh1b are not interchangeable, since they work directionally and have distinct functions. Although in the URL atoh1a activates the expression of neurod1 in intermediate, non-proliferative precursors [35], neurod1 expression is not detected in the zebrafish LRL before the 48hpf, implying that atoh1b is the one defining LRL intermediate precursors rather than neurod1 during early LRL-derived neurogenesis.…”

Heterochronic Developmental Shifts Underlying Squamate Cerebellar Diversity Unveil the Key Features of Amniote Cerebellogenesis

“…Despite the overall conserved progenitor domains and salient physiological and morphological features of cerebellar GCs and PCs across vertebrates (Altman and Bayer, 1997), modifications in their developmental programs have been linked to the remarkable degree of cerebellar complexity achieved during vertebrate radiation in terms of both magnitude and spatial arrangement of neurons and foliation pattern. In this perspective, the absence of a typical EGL-defined as a distinct progenitor population covering the cerebellar pial surface and expressing Atoh1in chondrichthyans and teleosts, but also the presence of a distinct, non-proliferative EGL in amphibians, indicate that the SHH-induced transit-amplifying phase in GCPs constitutes a hallmark of birds and mammals (Rodríguez-Moldes et al, 2008;Chaplin et al, 2010;Butts et al, 2014a;Pose-Méndez et al, 2016;Iulianella et al, 2019), likely allowing a massive GC production in a restricted developmental time window (Chaplin et al, 2010;Iulianella et al, 2019). In contrast, owing to the undetermined growth that characterizes the brain of anamniotes, some bony fishes and most likely chondrichthyans achieve extremely folded structures through continuous addition of GCs from stem progenitor pools throughout life (Candal et al, 2005;Zupanc et al, 2005;Rodríguez-Moldes et al, 2008;Chaplin et al, 2010;Kaslin et al, 2013;Butts et al, 2014b).…”

Atonal bHLH transcription factor 1 is an important factor for maintaining the balance of cell proliferation and differentiation in tumorigenesis (Review)

“…During embryonic brain development, ATOH1 is expressed in the dorsal hindbrain neuro epithelium, rhombic lip and the developing cerebellum (15,67). These ATOH1-dependent neurons are required for the generation of dorsal commissural interneurons (68) and brainstem respiratory nuclei, and the development of cerebellar granule cell lineages (18,69). Unlike MCs, in which ATOH1 is expressed in both progenitor and mature cells, ATOH1 expression persists during granule cell lineage development and in cerebellar granule cell precursors, but disappears during differentiation and migration from the external granule layer (EGL) to the internal granule layer (IGL; Fig.…”