Introducing the brain: healthy brain development (Introduction)

by David Turell , Tuesday, October 22, 2024, 19:52 (9 days ago) @ David Turell

From this process removing cilia in neurons:

https://www.the-scientist.com/new-cilia-disassembly-pathway-revealed-in-maturing-neuron...

"Despite their initial description 180 years ago, scientists for many years failed to understand the significance of the lone hair-like structures that extend from the surface of many cell types, including epithelial cells and neurons. Known as primary cilia, the physical differences between these immotile organelles and fluid-propelling motile cilia were not apparent. In the 1950s, transmission electron microscopy enabled researchers to distinguish the ultrastructure of these two forms of cilia and how primary cilia function in human health and disease.

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"Although numerous processes within the brain involve primary cilia, researchers understand very little about how modifications to the organelle’s ultrastructure affect neurodevelopment. Immature granule cells (GCs), which become the most abundant neuron type within the adult brain, offer a unique opportunity to answer this question.

"During development, the ligand sonic hedgehog (SHH) binds to receptors on the primary cilia of progenitor GCs, leading to the cells’ proliferation, differentiation, and migration to deeper layers of the cerebellum.4 But, once the differentiation stage begins, the cells stop responding to SHH. Additionally, immunofluorescence analysis has revealed that differentiating GCs have fewer and shorter cilia than their immature counterparts, with adult GCs rarely possessing these structures. This suggests that these cells disassemble their cilia during maturation. However, examining enough of these organelles to fully characterize this disassembly process presented a challenge for the researchers.

“'Cilia are hard to find if you are doing conventional EM,” said Ott. “They are low-frequency structures. There is one cilium per cell.”

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"Ott and her team determined that primary cilia permanently disassemble as GC progenitors differentiate. Given that this disassembly occurs in postmitotic cells, the researchers named this process cilia deconstruction to distinguish it from the transient cilia disassembly that occurs prior to cell division.

"While examining the ultrastructure of the primary cilia during cilia deconstruction, the researchers observed that many differentiating GCs possessed short cilia that were completely enclosed within a membranous compartment in their cytoplasm. This concealed these disassembling structures from stimuli in the extracellular environment, such as SHH.

"During cilia deconstruction, Ott and her team also noted that mother centrioles, which are responsible for the initial formation of cilia, ultimately dock at the plasma membrane but remain unciliated. This surprised the researchers as scientists have only observed a few examples of centrioles docking without forming cilium. The researchers detected novel deconstruction intermediates that were different from those observed during premitotic cilia disassembly, suggesting distinct processes. However, the team was unable to order the intermediates into a single linear pathway. Instead, they suggested that there are several cilia deconstruction routes possible that could generate unciliated adult GCs with docked mother centrioles."

Comment: this is discovery in process, not fully understood. It adds to the extraordinary complexity of the brain.