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 cellular mechanism for the growth and maintenance of dendritic arborization 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 al-tered subunit composition and found that increasing NF-H and/or NF-M inhibited dendritic arborization, whereas increasing NF-L alleviated this inhibition. Ex-amination of cytoskeletal organization revealed that in-creasing NF-H and/or NF-M caused NF aggregation and dissociation of the NF network from the microtu-bule (MT) network. Increasing NF-H or NF-H together with NF-M further reduced NFs from dendrites. How-ever, these changes were reversed by elevating the level of NF-L with either NF-H or NF-M. Thus, NF-L antag-onizes NF-H and NF-M in organizing the NF network and maintaining a lower ratio of NF-H and NF-M to NF-L is critical for the growth of complex dendritic trees in motor neurons. N eurons are polarized cells that receive and inte-grate synaptic input on the surface of their den-drites and cell bodies, and conduct action poten-tials to distal targets via their axons. Ample evidence indicates that the neuronal cytoskeleton plays important roles in the development of neuronal polarity (Cacere