Transcriptional regulation of vertebrate axon guidance and synapse formation

Abstract

Recent studies indicate that transcription factors have a crucial role in regulating axon guidance and synapse formation. Many of these factors act by regulating the response of neurons to guidance and synaptogenic cues. Islet 2 (ISL2), ZIC2, chick brain factor 1 (CBF1) and CBF2 are transcription factors that have been implicated in retinotectal patterning. ISL2 and ZIC2 appear to exert their effects by regulating EphB2 expression. CBF1 and CBF2 seem to exert their effects by regulating ephrin A–EphA signalling. ISL1, LIM1, LHX3 and LMX1B are LIM homeobox transcription factors that are implicated in the development of motor neuron projections. These factors are likely to affect axonal trajectories by influencing signalling by ephrins, semaphorins and fibroblast growth factors. Neurogenin 2, LIM domain only 4 (LMO4) and neurodifferentiation D2 (NeuroD2) have an important role in patterning thalamocortical axons. LMO4 and NeuroD2 are expressed in the postnatal cortex and mediate the activity-dependent refinement of thalamocortical axon terminals. Many of the transcription factors that affect axon guidance act by regulating the expression of ephrin and Eph receptor genes. Several transcription factors have been implicated in synapse formation, maturation and elimination. Cyclic AMP-response element binding protein (CREB) and NeuroD2 are involved in synapse formation and maturation. Myocyte enhancer factor 2 (MEF2) and neurogenin 3 appear to be involved in synapse elimination. These factors act in part by regulating the responsiveness of neurons to neurotransmitters.