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

Simone Macrì,Nicolas Di-Poï

doi:10.3389/fcell.2020.593377

Simone Macrì, Nicolas Di-Poï

Open Access

https://doi.org/10.3389/fcell.2020.593377

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Abstract

Despite a remarkable conservation of architecture and function, the cerebellum of vertebrates shows extensive variation in morphology, size, and foliation pattern. These features make this brain subdivision a powerful model to investigate the evolutionary developmental mechanisms underlying neuroanatomical complexity both within and between anamniote and amniote species. Here, we fill a major evolutionary gap by characterizing the developing cerebellum in two non-avian reptile species—bearded dragon lizard and African house snake—representative of extreme cerebellar morphologies and neuronal arrangement patterns found in squamates. Our data suggest that developmental strategies regarded as exclusive hallmark of birds and mammals, including transit amplification in an external granule layer (EGL) and Sonic hedgehog expression by underlying Purkinje cells (PCs), contribute to squamate cerebellogenesis independently from foliation pattern. Furthermore, direct comparison of our models suggests the key importance of spatiotemporal patterning and dynamic interaction between granule cells and PCs in defining cortical organization. Especially, the observed heterochronic shifts in early cerebellogenesis events, including upper rhombic lip progenitor activity and EGL maintenance, are strongly expected to affect the dynamics of molecular interaction between neuronal cell types in snakes. Altogether, these findings help clarifying some of the morphogenetic and molecular underpinnings of amniote cerebellar corticogenesis, but also suggest new potential molecular mechanisms underlying cerebellar complexity in squamates. Furthermore, squamate models analyzed here are revealed as key animal models to further understand mechanisms of brain organization.

Highlights

The cerebellum is a prominent feature of the vertebrate hindbrain that varies extensively in terms of relative size and morphology across major vertebrate groups, and in closely related species with distinct ecological and behavioral strategies (Voogd and Glickstein, 1998; Butler and Hodos, 2005; Striedter, 2005; Macrì et al, 2019)
Despite the overall conserved progenitor domains and salient physiological and morphological features of cerebellar granule cells (GCs) and Purkinje cells (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
The absence of a typical external granule layer (EGL)—defined as a distinct progenitor population covering the cerebellar pial surface and expressing atonal bHLH transcription factor 1 (Atoh1)— in chondrichthyans and teleosts, and the presence of a distinct, non-proliferative EGL in amphibians, indicate that the Sonic hedgehog (SHH)-induced transit-amplifying phase in GC precursors (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)

Summary

Introduction

The cerebellum is a prominent feature of the vertebrate hindbrain that varies extensively in terms of relative size and morphology across major vertebrate groups, and in closely related species with distinct ecological and behavioral strategies (Voogd and Glickstein, 1998; Butler and Hodos, 2005; Striedter, 2005; Macrì et al, 2019). It reaches the highest level of morphological complexity in birds, mammals, and in some cartilaginous and bony fishes, in which a remarkable. Cerebellar development is well-known to rely on the spatiotemporal activity patterns of several key signaling pathways, the exact molecular and evolutionary mechanisms that govern the generation and arrangement of major neuronal types and foliation pattern are only partially resolved

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