The molecules and mechanisms that govern the growth and patterning of neurites (neural processes such as axons or dendrites) are poorly understood. However, two papers in this issue provide important new insights into the control of these essential aspects of nervous system development.
On p. 3405, Alun Davies and colleagues report that the promotion of neurite growth from mouse sensory neurons by brain-derived neurotrophic factor (BDNF) involves an abrupt developmental switch in how nuclear factor kappa-B (NF-κB) signalling(which promotes neurite growth) is activated. Before birth, the researchers report, BDNF activates the transcription factor NF-κB by an atypical mechanism that involves tyrosine phosphorylation of the inhibitor IκBα by Src family kinases and its subsequent dissociation from NF-κB. At this developmental time, BDNF also dephosphorylates the p65 subunit of NF-κB at serine 536; activated NF-κB that is phosphorylated at Ser536 inhibits rather than promotes neurite growth. Immediately after birth, however, BDNF-promoted neurite growth involves BDNF-independent constitutive activation of NF-κB signalling through serine phosphorylation of IκBα and constitutive dephosphorylation of p65. These results, the researchers suggest, reveal that a single signalling network can be activated in different ways to generate identical cellular responses to the same extracellular signal during neural development.
On p. 3475, Donald van Meyel and colleagues report that Turtle (Tutl), a conserved immunoglobulin superfamily protein, controls dendrite branching and dendrite self-avoidance in developing Drosophila sensory neurons. These neurons form dendritic trees with cell-type-specific patterns of arborisation in which dendrite branches from the same neuron avoid each other. Recognition molecules on the surfaces of dendrites influence arborisation patterns by promoting attractive, repulsive or adhesive responses to specific cues. The researchers report that Tutl, a transmembrane protein, is expressed on developing neurons in the Drosophila peripheral nervous system. In in vivo loss- and gain-of-function experiments, they show that Tutl restricts branching in neurons with simple arbors and promotes dendrite self-avoidance in neurons with highly complex arbors. Finally, they show that the cytoplasmic tail of Tutl is not needed for the control of dendrite branching. Thus, they suggest,Tutl might influence dendrite arborisation patterns by acting as a ligand or a co-receptor for an unidentified recognition molecule.