The role of FGF3 in the guidance of prethalamic GABAergic axons

Abstract

Abstract The thalamus plays a crucial role in ensuring faithful transfer of sensory information, except olfactory signals, to corresponding cortical areas. However, thalamic function is not simply restricted to relaying information to and from the cerebral cortex. The ability to modulate the flow of sensory information is supported by a second abundant neuronal type in the prethalamus, the inhibitory GABAergic neurons, which project inhibitory GABAergic axons to dorsal thalamic glutamatergic neurons. Here, expression analyses reveal that morphogen fibroblast growth factor (FGF)-3 is expressed in the chick hypothalamus during the trajectory of pioneer prethalamic axons. Then, using in vitro analyses in chick explants, we identify a chemorepellent effect of FGF3 on nearby prethalamic axons. Moreover, inhibition of FGF3 guidance functions indicates that FGF3 signaling is necessary for the correct navigation of prethalamic axons. To test which downstream pathway is involved in the navigation of prethalamic axons, we used expression analyses and loss of function studies. We find that FGF3 mediates prethalamic axonal guidance through the FGFR1 downstream pathway. Together, these results suggest that FGF3 expressed in the hypothalamus functions as a chemorepellent molecule to direct the pathway selection of neighbouring GABAergic axons.