Dataset Information

Absence of an external germinal layer in zebrafish and shark reveals a distinct, anamniote ground plan of cerebellum development.

ABSTRACT: The granule cell layer of the cerebellum comprises the largest population of neurons in the vertebrate CNS. In amniotes, its precursors undergo a unique phase of transit amplification, regulated by Sonic hedgehog. They do so within a prominent but transient secondary proliferative epithelium, the external germinal layer, which is formed by tangential migration of precursor cells from the rhombic lip. This behavior is a hallmark of bird and mammal cerebellum development. Despite its significance for both development and disease, it is unclear whether an external germinal layer is a requirement for granule cell production or an expedient of transit amplification. Evidence for its existence in more basal vertebrates is contradictory. We therefore examined cerebellum development in the zebrafish, specifically in relation to the expression of the basic helix-loop-helix gene Atonal 1, which definitively characterizes granule cell precursors. The expression of Atoh1a-Atoh1c, in combination with patterns of proliferation and fate maps, define precursor pools at the rhombic lip and cerebellar midline but demonstrate that an external germinal layer is absent. Sonic hedgehog signaling is correspondingly absent in the zebrafish cerebellum. Sustained roof-plate-derived signals suggest that, in the absence of transit amplification, primary granule cell precursor pools are maintained throughout development. To determine whether this pattern is specific to zebrafish or reflects a more general anamniote organization, we examined the expression of similar genes in the dogfish, Scylliorhinus canicula. We show that these anamniotes share a common ground plan of granule cell production that does not include an external germinal layer.

SUBMITTER: Chaplin N

PROVIDER: S-EPMC2883741 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:In mammals and other tetrapods, a multinuclear forebrain structure, called the amygdala, forms the neuroregulatory core essential for emotion, cognition, and social behavior. Currently, higher circuits of affective behavior in anamniote non-tetrapod vertebrates ("fishes") are poorly understood, preventing a comprehensive understanding of amygdala evolution. Through molecular characterization and evolutionary-developmental considerations, we delineated the complex amygdala ground plan of zebrafish, whose everted telencephalon has made comparisons to the evaginated forebrains of tetrapods challenging. In this radical paradigm, thirteen telencephalic territories constitute the zebrafish amygdaloid complex and each territory is distinguished by conserved molecular properties and structure-functional relationships with other amygdaloid structures. Central to our paradigm, the study identifies the teleostean amygdaloid nucleus of the lateral olfactory tract (nLOT), an olfactory integrative structure that links dopaminergic telencephalic groups to the amygdala alongside redefining the putative zebrafish olfactory pallium ("Dp"). Molecular characteristics such as the distribution of substance P and the calcium-binding proteins parvalbumin (PV) and calretinin (CR) indicate, that the zebrafish extended centromedial (autonomic and reproductive) amygdala is predominantly located in the GABAergic and isl1-negative territory. Like in tetrapods, medial amygdaloid (MeA) nuclei are defined by the presence of substance P immunoreactive fibers and calretinin-positive neurons, whereas central amygdaloid (CeA) nuclei lack these characteristics. A detailed comparison of lhx5-driven and vGLut2a-driven GFP in transgenic reporter lines revealed ancestral topological relationships between the thalamic eminence (EmT), the medial amygdala (MeA), the nLOT, and the integrative olfactory pallium. Thus, the study explains how the zebrafish amygdala and the complexly everted telencephalon topologically relate to the corresponding structures in mammals indicating that an elaborate amygdala ground plan evolved early in vertebrates, in a common ancestor of teleosts and tetrapods.

Project description:BackgroundThe Notch signalling pathway plays crucial roles in neural development, functioning by preventing premature differentiation and promotion of glial cell fates. In the developing cerebellum Notch pathway components are expressed in granule neuron progenitors of the external germinal layer (EGL) but the precise function of Notch in these cells is unclear. The Hedgehog pathway is also crucial in cerebellar development, mainly via control of the cell cycle, and persistent activation of the pathways leads to the cerebellar tumour medulloblastoma. Interactions between Hedgehog and Notch have been reported in normal brain development as well as in Hedgehog pathway induced medulloblastoma but the molecular details of this interaction are not known and we investigate here the role of Notch signalling in the development of the EGL and the intersection between the two pathways in cerebellar granule neuron progenitors and in medulloblastoma.ResultsRBP-J is the major downstream effector of all four mammalian Notch receptors and the RBP-J conditional mouse facilitates inactivation of canonical Notch signals. Patched1 is a negative regulator of Hedgehog signalling and the Patched1 conditional mouse is widely used to activate Hedgehog signalling via Patched1 deletion in specific cell types. The conditional mouse lines were crossed with a Math1-Cre line to delete the two genes in granule neuron progenitors from embryonic day 10.5. While deletion of only Patched1 as well as Patched1 together with RBP-J leads to formation of medulloblastoma concomitant with disorganisation of cell layers, loss of RBP-J from granule neuron progenitors has no obvious effect on overall cerebellar morphology or differentiation and maturation of the different cerebellar cell types.ConclusionsOur results suggest that even though Notch signalling has been shown to play important roles in cerebellar development, signalling via RBP-J is surprisingly not required in granule neuron progenitors. Furthermore, RBP-J inactivation in these cells does not influence the formation of medulloblastoma initiated by Hedgehog pathway activation. This may suggest a requirement of Notch in cerebellar development at a different developmental stage or in a different cell type than examined here - for example, in the neural stem cells of the ventricular zone. In addition, it remains a possibility that, in granule neuron progenitors, Notch may signal via an alternative pathway without the requirement for RBP-J.

Dataset Information

Absence of an external germinal layer in zebrafish and shark reveals a distinct, anamniote ground plan of cerebellum development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets