Fig 6. Wiring algorithm underlying the development, homeostasis, and regeneration of planar-polarity–selective synaptogenesis and neuronal directional tuning.

(A) Left, schematic description of the wiring algorithm using a wild-type horizontal neuromast as an example. In this and all subsequent panels, cells are color-coded: rcHCs/Emx2(+) (light blue), crHCs/Emx2(-) (light green); eccentric black dots indicate hair cell orientation. rcLANs (dark blue), crLANs (red). Arrows (green) indicate attractive interactions (stronger as solid lines and weaker as dotted lines), and circle-pointed lines (orange) indicate repulsive interactions. Right, schematic description of interactions between cells. (B) Scheme of the constituent cells. (C) Scheme of a situation of a chronically solitary axon, which becomes nonselective because the absence of the converse synapses eliminate the repulsive signals. (D) Scheme of an acutely solitary axon, which becomes transiently nonselective because the regeneration of the converse synapses recreates the repulsive signals to push the promiscuous axon to selectivity. Jagged arrow (purple) indicates axon damage. (E) Situation of axon damage and regeneration. Initially during regeneration, axons explore the presynaptic field and transiently interact with hair cells, but eventually the wiring algorithm is recreated following the same rules controlling selectivity during circuit development. (F) Situation of hair cell loss and regeneration. Initially during hair cell regeneration, axons explore the presynaptic field and transiently interact with hair cells, but once hair cells mature, the wiring algorithm is recreated following the same rules controlling selectivity during circuit development. (G) Situation of homogeneously oriented hair cell upon loss of Emx2 activity. The wiring algorithm becomes asymmetric, directing one axonal population to synapses with every hair cell and inhibiting the other axons from establishing any synapse. (H) Situation of misoriented hair cell upon loss of Vangl2. The wiring algorithm remains normal because it operates independently of coherent planar polarity. Therefore, synaptic selectivity for Emx2(+) and Emx2(-) hair cells occurs normally. crHC, caudorostral HC; crLAN, caudorostral LAN; HC, hair cell; LAN, lateralis afferent neuron; rcHC, rostrocaudal HC; rcLAN, rostrocaudal LAN; Vangl2, van gogh-like 2.