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Lack of lipid phosphate phosphatase‐3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth
Author(s) -
SánchezSánchez Roberto,
MoralesLázaro Sara L.,
Baizabal JoséManuel,
Sunkara Manjula,
Morris Andrew J.,
EscalanteAlcalde Diana
Publication year - 2012
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23779
Subject(s) - neurite , lysophosphatidic acid , biology , microbiology and biotechnology , embryonic stem cell , cellular differentiation , neural stem cell , neurogenesis , stem cell , progenitor cell , in vitro , biochemistry , receptor , gene
Background: Bioactive lipids such as lysophosphatidic acid (LPA) and sphingosine‐1‐phosphate (S1P) have been recently described as important regulators of pluripotency and differentiation of embryonic stem (ES) cells and neural progenitors. Due to the early lethality of LPP3, an enzyme that regulates the levels and biological activities of the aforementioned lipids, it has been difficult to assess its participation in early neural differentiation and neuritogenesis. Results: We find that Ppap2b −/− ( Lpp 3 −/− ) ES cells differentiated in vitro into spinal neurons show a considerable reduction in the amount of neural precursors and young neurons formed. In addition, differentiated Lpp3 −/− neurons exhibit impaired neurite outgrowth. Surprisingly, when Lpp3 −/− ES cells were differentiated, an unexpected appearance of smooth muscle actin‐positive cells was observed, an event that was partially dependent upon phosphorylated sphingosines. Conclusions: Our data show that LPP3 plays a fundamental role during spinal neuron differentiation from ES and that it also participates in regulating neurite and axon outgrowth. Developmental Dynamics 241:953–964, 2012. © 2012 Wiley Periodicals, Inc.