Protein degradation shapes developmental tempo in mouse and human neural progenitors
Nakanoh, S.; Stamataki, D.; Garcia-Perez, L.; Azzi, C.; Carr, H. L.; Pokhilko, A.; Howell, S.; Yu, L.; Skehel, M.; Oxley, D.; Andrews, S.; Briscoe, J.; Rayon, T.
Show abstract
The pace of embryonic development differs markedly across mammalian species, yet the molecular mechanisms underlying these tempo differences remain largely unknown. Here, we systematically compared protein dynamics in mouse and human neural progenitors (NPs) and examined how protein stability influences developmental timing. We find that mouse NPs exhibit faster protein production and degradation than human NPs. Human NPs display broadly increased protein half-lives, independent of cellular compartment or protein function, and this difference persists in post-mitotic neurons. Consistent with this, proteasomal activity is lower in human embryonic spinal cord and stem cell-derived neural progenitors than mouse, correlating with reduced expression of proteasome-associated proteins. Functionally, accelerating the degradation of the key transcriptional repressor IRX3 in mouse NPs speeds the activation of its target gene, providing causal evidence that protein turnover modulates developmental tempo. These results reveal that species-specific regulation of protein degradation shapes the timing of neural development and suggest that evolutionary tuning of proteasomal activity contributes to differences in embryonic developmental pace.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Surfaceome dynamics during neuronal development and synaptic plasticity reveal system-wide surfaceome reorganization independent of global proteostasis 96%
- FICD activity and AMPylation remodelling modulate human neurogenesis. 96%
- Immunoproximity biotinylation reveals the axon initial segment proteome 95%
Similar papers in this journal
- Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids 95%
- SUMO Activated Target Traps (SATTs) enable the identification of a comprehensive E3-specific SUMO proteome. 95%
- Proteome-wide computational analyses reveal links between protein condensate formation and RNA biology 94%
Similar papers in this journal
- Proteomic and functional comparison between human induced and embryonic stem cells 96%
- Maintenance of neuronal TDP-43 expression requires axonal lysosome transport 95%
- An automated high-content synaptic phenotyping platform in human neurons and astrocytes reveals a role for BET proteins in synapse assembly 95%
Similar papers in this journal
- Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing 94%
- Pore engineering as a general strategy to improve protein-based enzyme nanoreactor performance 93%
- Synthetic Rewiring of Virus-Like Particles via Circular Permutation Enables Modular Peptide Display and Protein Encapsulation 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.