M2-like cells from the macrophage lineage might play a central role in closure of the embryonic neural tube

Abstract

Herein it is hypothesized that M2-like macrophages or pre-macrophages of fetal origin might play a central role in development and closure of the neural tube. Early in embryonic development, pre-macrophages arise from the fetal yolk sac and track through the bloodstream to reach diverse embryonic tissues, where they mature. Most of these macrophages exhibit an M2-like phenotype. The critical period for neural tube closure is contained within the period of yolk sac-derived pre-macrophage tracking and distribution, which poses a question: might these pre-macrophages or macrophages exert an influence on the closing neural tube? Evidence suggests that perturbations in macrophage polarization or M2 macrophage function might contribute to the failure of neural tube closure associated with diabetes mellitus, one carbon metabolism (including folic acid deficit), inositol, arachidonic acid, and sphingosine-1-phosphate, as well as in the teratogenicity of nitric acid, valproic acid, and fumonisin. The influence of each of these factors is interpreted in light of potential interactions with M2-like macrophages or macrophage progenitors on the developing neural tube. By placing these anti inflammatory macrophages at the center of various epigenetic, neurochemical, and signaling processes suspected to be involved in neural tube closure, potential associations are revealed between macrophages and embryonic structural developmental processes such as collagen and actin dynamics. The choice of this model is also an attempt to explain why some etiologies for failure of neural tube closure are rescued by folic acid, whereas other etiologies are rescued only by formate, inositol, or not at all.