An immunohistochemical study of the development of sensorimotor components of the early fetal human spinal cord

Sections from all spinal cord levels from 20 human fetuses, age range 7.5-17 gestational weeks (GW) were immunostained for non-phosphorylated neurofilaments (to reveal motoneurones, spinocerebellar neurones and other large neurones), the calcium-binding protein parvalbumin (large proprioreceptive afferents), growth-associated protein 43 kDa (growing axons), glial fibrillary acidic protein (radial glia), synaptophysin (synaptic terminals) the cell-cell recognition molecule ephrin A4 (EphA4) and the ETS transcription factor Er81 (subclasses of motoneurone and proprioreceptive neurone). Muscle afferents crossed the dorsal horn by 7.5 GW and innervated motoneurones by 9 GW. An alignment of glial fibres guided them from dorsal columns to ventral horn, at right angles to the radial glia. They continued to provide a dense innervation of motoneurone pools up to 17 GW. By 13 GW motoneurones were segregated into distinct columns, all of which expressed EphA4 although only certain lateral groups expressed Er81. However, Er81 expression was more widespread amongst dorsal root ganglion neurones. From 9 GW Clarke's column neurones were identified and by 14 GW were heavily innervated by parvalbumin-positive afferents whilst their efferent axons could be traced to the lateral funiculus. This investigation contributes towards a timetable for the functional development of human motor control and makes comparisons with well-studied rodent models.