Abstract 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. © 2008 Wiley‐Liss, Inc.