Human fetal hippocampal development: II. The neuronal cytoskeleton.

In this study of the developing human hippocampus, we monitor the timing of onset and the sequential patterns of expression of 11 developmentally regulated proteins that are important components of the neuronal cytoskeleton. Immunohistochemistry using well-characterized antibodies was conducted with fixed paraffin-embedded sections from hippocampi at various stages of fetal and postnatal development. At 9 weeks gestational age, immunoreactivity was evident for the microtubule-associated proteins (MAPs), MAP2 and MAP5, low molecular weight (Mr) neurofilament (NF) protein (NF-L), poorly phosphorylated mid-Mr NF protein (NF-M/P-), vimentin, and alpha-and beta-tubulins within the somatodendritic domain of neurons of the hippocampal plate. Weak immunoreactivity for moderately phosphorylated, high Mr NF protein (NF-H/P + + +), tau, and nestin was observed. Highly phosphorylated mid-Mr NF protein (NF-M/P + + +) and alpha-internexin were first detected at 15 weeks and highly phosphorylated, high Mr NF protein (NF-H/P+3) at 20 weeks. At 15 weeks, MAP2, MAP5, and tubulins were expressed in an "inside-out" gradient and in a gradient between hippocampal subfields with subiculum > ammonic subfields > dentate gyrus. These gradients paralleled the maturational gradients seen in cytoarchitectural and neuronal morphologic studies. The adult pattern of neuronal cytoskeletal protein expression in the hippocampus was attained by the second postnatal year for all proteins. Our findings demonstrate an elaborate orchestration of cytoskeletal protein expression within the hippocampus that is qualitatively similar to what is seen in other brain regions and in nonhuman species but which also has some important differences in timing and pattern. The differences in the developmentally regulated expression of neuronal cytoskeletal proteins in separate regions of the central nervous system (CNS) suggest that there are region-specific differences in composition and function of the neuronal cytoskeleton. These observations have implications for understanding the role of the neuronal cytoskeleton in the developing, mature, and diseased CNS.