Dataset Information

Proteasome-dependent protein degradation shapes developmental tempo in mouse and human neural progenitors

ABSTRACT: Developmental programs are conserved across mammals, but the developmental pace varies between species. Stem cell models have revealed that human neural progenitors develop more slowly than the mouse counterpart due to reduced protein degradation rates. Key questions remain about species-specific protein half-lives, its impact on overall protein levels, and the regulation of protein production and degradation during development. The effect of manipulating individual protein stability on developmental pace is also unclear. Here we analyzed protein production, degradation, and abundance in mouse and human neural progenitors using targeted protein labeling, proteomics, and functional genomics. We identified species differences in protein turnover and found that both active degradation influence tempo divergence between mouse and human. Moreover, proteolytic degradation of a key regulatory protein was shown to affect developmental pace. Our study stresses the role of protein degradation in controlling developmental tempo, with implications for phenotypic diversity across evolution.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

SUBMITTER: David Oxley

LAB HEAD: Teresa Rayon

PROVIDER: PXD053697 | Pride | 2026-07-14

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 32

Similar Datasets

Project description:Echinoderm microtubule (MT)-associated protein-like 1 (Eml1) is mutated in the HeCo mouse, which exhibits subcortical band heterotopia (SBH), a developmental malformation of the cerebral cortex. EML1 mutations are also found in human patients affected by severe ribbon-like heterotopia, associated with epilepsy and intellectual disability (1). Neural progenitors in the ventricular zone (VZ) of the developing cerebral cortex undergo precisely regulated divisions, and mitotic perturbations contribute to pathological mechanisms (2). Eml1 is expressed in the mouse VZ and ectopic progenitors are present in the mutant developing cortex, when Eml1 is absent, at early stages of development (1). Thus, Eml1 is likely to play a role in neural progenitors during cortical development. We performed cell and molecular biology assays aiming to elucidate the function of Eml1 in neural progenitors, and explored the VZ of the HeCo mutant in order to find morphological perturbations that might explain the initiation of SBH formation (3). As part of this study, we searched for Eml1 molecular partners by pull-downs from mouse cortical extracts at embryonic day E13.5 and mass spectrometry (MS) analyses in order to identify the molecular pathways in which the protein is involved (3). Eml1 is formed by an N-terminal region that contains a dimerization domain and a C-terminal region that forms a ‘tandem atypical propeller in EMLs’ (TAPE) domain. The isolated N-terminal domain strongly binds MTs, while the C-terminal domain preferentially binds tubulin, and its beta-propeller structure is thought also to mediate the interaction with other molecules (4,5). We focused for this study on the N-terminal part of the protein (amino acids 1-178). Future study will validate or elucidate new interactions by using the C-terminal domain and/or the full-length protein. The results obtained from the N terminal MS data, integrated with other experimental findings, allow us to insert Eml1 in a network of proteins that are likely to regulate the assembly and function of the mitotic spindle in neural progenitors (3). More precisely, we showed that the protein regulates MT dynamics and its loss leads to perturbations in metaphase spindle length, which in turn impact progenitor morphology and behavior (3). References 1. Kielar, M., et al. Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human. Nat. Neurosci. 17, 923–933 (2014). 2. Bizzotto, S., & Francis, F. Morphological and functional aspects of progenitors perturbed in cortical malformations. Front Cell Neurosci. 9, 30; 10.3389/fncel00030 (2015). 3. Bizzotto, S., et al. Eml1 loss impairs apical progenitor spindle length and soma shape in the developing cerebral cortex. 4. Richards, M. W., et al. Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical β-propeller domain. Proc. Natl. Acad. Sci. U.S.A. 111, 5195–5200 (2014). 5. Richards, M. W., et al. Microtubule association of EML proteins and the EML4-ALK variant 3 oncoprotein require an N-terminal trimerization domain. Biochem. J. 467, 529–536 (2015).

			Action	DRS
	Human-01_DIA.raw	Raw
	Human-02_DIA.raw	Raw
	Human-03_DIA.raw	Raw
	Human-04_DIA.raw	Raw
	Human-05_DIA.raw	Raw

Dataset Information

Proteasome-dependent protein degradation shapes developmental tempo in mouse and human neural progenitors

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets