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mSEL‐1L deficiency affects vasculogenesis and neural stem cell lineage commitment
Author(s) -
Cardano Marina,
Diaferia Giuseppe R.,
Conti Luciano,
Baronchelli Simona,
Sessa Alessandro,
Broccoli Vania,
Barbieri Andrea,
De Blasio Pasquale,
Biunno Ida
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26153
Subject(s) - biology , microbiology and biotechnology , neural stem cell , embryonic stem cell , progenitor cell , vasculogenesis , progenitor , sox2 , lineage (genetic) , neurogenesis , neuroscience , stem cell , genetics , gene
mSEL‐1L is a highly conserved ER‐resident type I protein, involved in the degradation of misfolded peptides through the ubiquitin–proteasome system (UPS), a pathway known to control the plasticity of the vascular smooth muscle cells (VSMC) phenotype and survival. In this article, we demonstrate that mSEL‐1L deficiency interferes with the murine embryonic vascular network, showing particular irregularities in the intracranic and intersomitic neurovascular units and in the cerebral capillary microcirculation. During murine embryogenesis, mSEL‐1L is expressed in cerebral areas known to harbor progenitor neural cells, while in the adult brain the protein is specifically restricted to the stem cell niches, co‐localizing with Sox2 and Nestin. Null mice are characterized by important defects in the development of telenchephalic regions, revealing conspicuous aberration in neural stem cell lineage commitment. Moreover, mSEL‐1L depletion in vitro and in vivo appears to affect the harmonic differentiation of the NSCs, by negatively influencing the corticogenesis processes. Overall, the data presented suggests that the drastic phenotypic characteristics exhibited in mSEL‐1L null mice can, in part, be explained by the negative influence it plays on Notch1 signaling pathway.