Amniotic fluid (AF) and cerebrospinal fluid (CSF) are routinely sampled for biomarkers of diseases, including autism spectrum disorder (ASD). The cerebral cortex, which governs higher cognitive functions, initially develops from neural stem cells that interface with CSF-filled ventricles. Surprisingly little is known about how fluid-borne signals are distributed across the developing brain, or about the mechanisms by which changes in fluid composition actively instruct brain development.
Maria Lehtinen and her colleagues have demonstrated that AF and CSF distribute molecular signals to cerebral cortical progenitor cells to instruct and coordinate brain development1, 2. These findings suggest the possibility that deviations in fluid composition caused by environmental factors, including those introduced by maternal health, can have severe consequences for later stages of brain development. Lehtinen hypothesizes that, in genetically predisposed mothers, fever during the early stages of fetal brain development may lead to increased concentrations of harmful signals in the AF and CSF. The presence of such signals could increase the likelihood that the child will develop ASD and affect the severity of the symptoms.
Lehtinen and her team plan to test their hypothesis by using polyinosinic:polycytidylic acid (PolyI:C) to induce maternal immune activation in 16p11.2 deletion mice. PolyI:C treatment leads to fever induction and is known to promote cerebral cortical enlargement in the fetal brain and ASD-like behaviors in the adult offspring of wild-type mice. The researchers will test for changes in AF and CSF composition in the fetuses of 16p11.2 pregnant mice treated with PolyI:C and examine how these changes disrupt cortical progenitor cell proliferation and fetal brain development. This research will help to identify how fluid-borne signals synergize with permissive genetic backgrounds to trigger ASD.