ANTAGONISTIC ROLES OF NEUROFILAMENT SUBUNITS NF-H AND NF-M AGAINST NF-L IN SHAPING DENDRITIC ARBORIZATION IN SPINAL MOTOR-NEURONS

Dendrites play important roles in neuronal function. However, the cell ular mechanism for the growth and maintenance of dendritic arborizatio n is unclear. Neurofilaments (NFs), a major component of the neuronal cytoskeleton, are composed of three polypeptide subunits, NF-H, NF-M, and NF-L, and are abundant in large dendritic trees. By overexpressing each of the three NF subunits in transgenic mice, we altered subunit composition and found that increasing NF-H and/or NF-M inhibited dendr itic arborization, whereas increasing NF-L alleviated this inhibition. Examination of cytoskeletal organization revealed that increasing NF- H and/or NF-M caused NF aggregation and dissociation of the NF network from the microtubule (MT) network. Increasing NF-H or NF-H together w ith NF-M further reduced NFs from dendrites. However, these changes we re reversed by elevating the level of NF-L with either NF-H or NF-M. T hus, NF-L antagonizes NF-H and NF-M in organizing the NF network and m aintaining a lower ratio of NF-H and NF-M to NF-L is critical for the growth of complex dendritic trees in motor neurons.