toplogo
Sign In

Identification of a Novel Subset of Cerebellar Nuclei Neurons Originating from the Mesencephalon in Mice


Core Concepts
A subset of cerebellar nuclei neurons originates from an extrinsic germinal zone, potentially the mesencephalon, independently of the known cerebellar primordium germinal zones.
Abstract
The study investigates a previously unrecognized subset of cerebellar nuclei (CN) neurons that do not originate from the well-established germinal zones of the cerebellar primordium. Key findings: A subset of CN neurons expressing SNCA, OTX2, MEIS2, and p75NTR are located in the rostroventral region of the nuclear transitory zone (NTZ) in the cerebellar primordium, distinct from the rhombic lip-derived CN neurons. The SNCA+/OTX2+/MEIS2+/p75NTR+ CN neurons do not originate from the cerebellar ventricular zone or rhombic lip, as confirmed using Otx2-GFP and Atoh1-/- mice. Embryonic DiI labeling experiments suggest the mesencephalon as a potential extrinsic germinal zone for this novel subset of CN neurons. The SNCA+/OTX2+/MEIS2+/p75NTR+ CN neurons are present in the absence of Atoh1, indicating their development is independent of the rhombic lip-derived CN neurons. These results reveal the existence of a previously unidentified germinal zone, potentially the mesencephalon, that gives rise to a distinct subset of CN neurons during early cerebellar development.
Stats
The number of OTX2 positive cells in the cerebellar primordium increased slightly from E12 to E15, with significant differences observed between E12 and E14 (p<0.01), E12 and E15 (p<0.001), as well as E13 and E15 (p<0.05). An increase in the number of SNCA and OTX2 positive cells was observed at E14 compared to E12 (p<0.05).
Quotes
"Our findings indicate that a subset of CN neurons expressing α-synuclein (SNCA), OTX2, MEIS2, and p75NTR (NGFR) are located in the rostro-ventral (rv) region of the nuclear transitory zone (NTZ), while CN neurons derived from the rhombic lip are positioned in the caudo-dorsal (cd) area of the NTZ in the cerebellar primordium." "Utilizing Otx2-GFP and Atoh1-/- mice, we have determined that these cells do not originate from the germinal zone of the cerebellar primordium." "Our data suggest that the mesencephalon could represent a third germinal zone and, as such, the origin of previously unrecognized neurons that contribute to CN formation and development."

Deeper Inquiries

What are the specific developmental and functional roles of the SNCA+/OTX2+/MEIS2+/p75NTR+ cerebellar nuclei neurons originating from the mesencephalon

The SNCA+/OTX2+/MEIS2+/p75NTR+ cerebellar nuclei neurons originating from the mesencephalon play crucial developmental and functional roles in the cerebellum. These neurons are involved in the early stages of cerebellar development, contributing to the formation of the cerebellar nuclei. SNCA (alpha-synuclein) is a protein associated with neuronal development and function, while OTX2 is a transcription factor essential for brain and midbrain development. MEIS2 is another transcription factor that regulates neuronal development, and p75NTR is a receptor involved in neuronal proliferation and differentiation. Together, these proteins indicate the specific identity and function of this subset of cerebellar nuclei neurons. In terms of function, these neurons likely contribute to the regulation of motor coordination, balance, and motor learning, which are key functions of the cerebellum. They may also play a role in modulating cognitive functions and emotional processing, given the interconnected nature of the cerebellum with various brain regions. Additionally, these neurons may have specific roles in synaptic transmission, plasticity, and network connectivity within the cerebellar circuitry.

How do the mesencephalon-derived cerebellar nuclei neurons interact with and integrate into the broader cerebellar circuitry compared to the rhombic lip-derived neurons

Mesencephalon-derived cerebellar nuclei neurons, such as the SNCA+/OTX2+/MEIS2+/p75NTR+ subset, interact and integrate into the broader cerebellar circuitry in a distinct manner compared to rhombic lip-derived neurons. While rhombic lip-derived neurons contribute to the glutamatergic projection neurons of the cerebellar nuclei, the mesencephalon-derived neurons may have unique properties and connectivity patterns. The mesencephalon-derived neurons may establish connections with specific regions of the cerebellum, such as the vermis or intermediate hemispheres, influencing motor control and coordination. They may also form connections with other brain regions outside the cerebellum, participating in broader neural circuits involved in motor planning, sensory integration, and cognitive processing. In terms of integration, mesencephalon-derived neurons may exhibit distinct synaptic properties, neurotransmitter release patterns, and plasticity mechanisms compared to rhombic lip-derived neurons. Their integration into the cerebellar circuitry may involve specific interactions with Purkinje cells, mossy fibers, and other cerebellar nuclei neurons, contributing to the overall function and coordination of the cerebellum.

Given the potential mesencephalic origin of this novel cerebellar nuclei neuron subset, how might this finding inform our understanding of the evolutionary origins and developmental patterning of the cerebellum

The potential mesencephalic origin of the novel cerebellar nuclei neuron subset sheds light on the evolutionary origins and developmental patterning of the cerebellum. This finding suggests a previously unrecognized germinal zone in the mesencephalon, indicating a more complex and diverse developmental process in cerebellar neurogenesis. From an evolutionary perspective, the identification of mesencephalon-derived cerebellar nuclei neurons implies a deeper evolutionary history and conservation of developmental mechanisms in the cerebellum. It suggests that the cerebellum may have evolved through the integration of neural populations from multiple brain regions, highlighting the intricate interplay between different brain structures during evolution. Furthermore, understanding the mesencephalic origin of these neurons provides insights into the molecular and cellular mechanisms underlying cerebellar development. It opens up new avenues for research into the regulatory pathways, genetic factors, and signaling molecules that govern the formation and differentiation of cerebellar nuclei neurons, contributing to our broader understanding of brain development and evolution.
0