Low-density lipoproteins from embryonic cerebrospinal fluid are required for neural differentiation.
During development, embryonic cerebrospinal fluid(E-CSF) is involved in cell survival, proliferation, and neurogenesis of the neuroepithelial progenitor cells. We have recently identified a complex pattern of proteins in chick and rat E-CSF, which include apolipoproteins. Apolipoproteins play a critical role in the function of lipoproteins by interacting with receptors to deliver the lipid cargo to target cells. However, the function of these E-CSF apolipoproteins is unclear. Here, we characterized the chick E-CSF lipoprotein profile and analyzed the role of its lipoprotein fractions in neural differentiation. We found that the lipoprotein pattern of chick E-CSF differed significantly from that of adult plasma, with a major proportion of apoB-containing lipoproteins. Further, supplementation of lipoprotein-depleted fraction with E-CSF very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) resulted in 25% and 60%, respectively, of the neurogenesis induced by the whole E-CSF in chick neuroepithelium explants, whereas high-density lipoproteins caused the lowest induction. We further investigated the potential role of E-CSF LDL in vivo by analyzing neural differentiation in the neuroepithelium of wild-type (WT) and LDL receptor-knockout (LDLR KO) mouse embryos. E-CSF lipids were mainly associated with LDL in both WT and LDLR KO mice, and the latter exhibited a substantial increase in LDL lipids compared with WT mice. Externally, LDLR KO embryos were apparently normal, and they exhibited up to 26% reduction in the number of neural differentiating cells in comparison with WT mice, although this finding was not statistically significant. These data strongly suggest that E-CSF LDL plays a critical role during early neural differentiation.
Parada
Carolina
C
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Escolà-Gil
Joan Carles
JC
Bueno
David
D
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002642:Chick Embryo / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D002645:Chickens / Q000097:blood / Q000134:cerebrospinal fluid* / Q000502:physiology; D005260:Female; D008077:Lipoproteins, LDL / Q000134:cerebrospinal fluid*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009924:Organ Culture Techniques; D011247:Pregnancy
D008077:Lipoproteins, LDL