Proteomics

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Embryonic cortical extract mass spectrometry to identify EML1 interactors


ABSTRACT: The cerebral cortex is a highly organized structure whose development depends on different progenitor cell types. These give rise to post-mitotic neurons that migrate across the developing cortical wall to their final positions in the cortical plate. Apical radial glia cells (aRGs) are the main progenitor type in early corticogenesis, responsible for the production of other progenitors, and regulating the final neuronal output. Abnormal behavior of aRG can severely impact corticogenesis resulting in cortical malformations. Mutations in the microtubule associated protein Eml1 lead to severe subcortical heterotopia, characterized by the presence of aberrantly located neurons beneath the normotopic cortex. Mutations in EML1/Eml1 have been reported in three families presenting severe atypical heterotopia, as well as in the Heterotopic cortex ‘HeCo’ spontaneous mouse mutant. In the latter, ectopically cycling aRGs were found cycling outside their normal proliferative ventricular zone (VZ) from early stages of corticogenesis (Croquelois et al., 2009, Kielar et al., 2014, Shaheen et al., 2017). Ectopic aRGs are likely to be responsible for the formation of the heterotopia. It is thus crucial to understand the role of Eml1 in aRGs to elucidate the physiological and pathological mechanisms causing aRGs to leave the VZ. The role of Eml1 in aRGs remains vastly unexplored. We have thus performed mass spectrometry with embryonic cortex lysates (E13.5) to shed light on the intracellular pathways and molecular mechanisms in which Eml1 could be involved. This data combined with other cell biology and biochemistry approaches will contribute to understand the role of this heterotopia protein at early stages of development.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Guillaume Arras  

LAB HEAD: Damarys Loew

PROVIDER: PXD012714 | Pride | 2019-06-20

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
C6509VM.msf Msf
C6509VM.raw Raw
C6510VM.msf Msf
C6510VM.raw Raw
C6513VM.msf Msf
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Publications


Apical radial glia (aRGs) are predominant progenitors during corticogenesis. Perturbing their function leads to cortical malformations, including subcortical heterotopia (SH), characterized by the presence of neurons below the cortex. EML1/Eml1 mutations lead to SH in patients, as well as to heterotopic cortex (HeCo) mutant mice. In HeCo mice, some aRGs are abnormally positioned away from the ventricular zone (VZ). Thus, unraveling EML1/Eml1 function will clarify mechanisms maintaining aRGs in t  ...[more]

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