The multiple decisions made by growth cones of RGCs as they navigate from the retina to the tectum in Xenopus embryos

Abstract

Retinal ganglion cells (RGCs) of Xenopus laevis send axons along a stereospecific pathway from the retina to their target the optic tectum. Viewed from the point of the growth cone, this journey is reflected by discrete processes of axon initiation, axon outgrowth, navigation, target recognition, and innervation. These processes are characterised by distinct signalling mechanisms that trigger dynamic changes in growth cone morphology and behavior. Here we review work primarily from our laboratory, examining these events from a cellular and molecular perspective, focusing on the roles of FGFs, netrins, receptors, and intracellular effectors.

Region-specific regulation of voltage-gated intrinsic currents in the developing optic tectum of theXenopustadpole

“…This program of development that we observed across the RC axis, in which both intrinsic excitability and levels of synaptic drive are increasing, is similar to what has been described to take place in neurons in the middle third of tectum between developmental stages 42-just after retinal ganglion cell axons have reached the tectum (Dingwell et al 2000) and have begun forming immature synapses onto the tectal neurons-and 45. During this time in development, both synaptic drive and intrinsic excitability tended to increase (Pratt and Aizenman 2007).…”

Region-specific regulation of voltage-gated intrinsic currents in the developing optic tectum of theXenopustadpole

“…This program of development that we observed across the RC axis, in which both intrinsic excitability and levels of synaptic drive are increasing, is similar to what has been described to take place in neurons in the middle third of tectum between developmental stages 42-just after retinal ganglion cell axons have reached the tectum (Dingwell et al 2000) and have begun forming immature synapses onto the tectal neurons-and 45. During this time in development, both synaptic drive and intrinsic excitability tended to increase (Pratt and Aizenman 2007).…”

Homeostatic Regulation of Intrinsic Excitability and Synaptic Transmission in a Developing Visual Circuit

“…Specifically, we focus on three periods of early development of the retinotectal circuit: stage 42/43, stages 44 -46, and stage 49 (see Materials and Methods for timing of stages). After RGC axons first reach their target tectum around developmental stage 39 (Holt, 1989;Dingwell et al, 2000), they begin to make functional synapses and convey visual information (stage 42/43). This is followed by a dynamic phase of synaptic formation and loss, as tectal cell dendrites grow and become more complex, and RGC axon terminals are highly motile (stages 44 -46) (Cline et al, 1997).…”

Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids

“…In addition, while RGC axons were capable of growth into varied assembloid models, RGCs extended longer axons into prosencephalic brain organoids, yet the number of RGC axons was increased within thalamic organoids. These observations suggest that the environment within thalamic organoids provides more suitable cues for RGCs to explore rather than quickly pass through, reminiscent of topographic mapping in the tectum when RGCs begin to enter the LGN and slow their growth and increase branching in the stages prior to refinement ( Dingwell et al., 2000 ; Godement and Mason, 1993 ). Overall, these results will provide a foundation for future studies of human RGC axonal outgrowth and the environmental cues that guide this pathfinding.…”

Region-specific regulation of voltage-gated intrinsic currents in the developing optic tectum of theXenopustadpole

“…This program of development that we observed across the RC axis, in which both intrinsic excitability and levels of synaptic drive are increasing, is similar to what has been described to take place in neurons in the middle third of tectum between developmental stages 42-just after retinal ganglion cell axons have reached the tectum (Dingwell et al 2000) and have begun forming immature synapses onto the tectal neurons-and 45. During this time in development, both synaptic drive and intrinsic excitability tended to increase (Pratt and Aizenman 2007).…”

Homeostatic Regulation of Intrinsic Excitability and Synaptic Transmission in a Developing Visual Circuit

“…Specifically, we focus on three periods of early development of the retinotectal circuit: stage 42/43, stages 44 -46, and stage 49 (see Materials and Methods for timing of stages). After RGC axons first reach their target tectum around developmental stage 39 (Holt, 1989;Dingwell et al, 2000), they begin to make functional synapses and convey visual information (stage 42/43). This is followed by a dynamic phase of synaptic formation and loss, as tectal cell dendrites grow and become more complex, and RGC axon terminals are highly motile (stages 44 -46) (Cline et al, 1997).…”

Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids

“…In addition, while RGC axons were capable of growth into varied assembloid models, RGCs extended longer axons into prosencephalic brain organoids, yet the number of RGC axons was increased within thalamic organoids. These observations suggest that the environment within thalamic organoids provides more suitable cues for RGCs to explore rather than quickly pass through, reminiscent of topographic mapping in the tectum when RGCs begin to enter the LGN and slow their growth and increase branching in the stages prior to refinement ( Dingwell et al., 2000 ; Godement and Mason, 1993 ). Overall, these results will provide a foundation for future studies of human RGC axonal outgrowth and the environmental cues that guide this pathfinding.…”

Region-specific regulation of voltage-gated intrinsic currents in the developing optic tectum of theXenopustadpole

“…This program of development that we observed across the RC axis, in which both intrinsic excitability and levels of synaptic drive are increasing, is similar to what has been described to take place in neurons in the middle third of tectum between developmental stages 42-just after retinal ganglion cell axons have reached the tectum (Dingwell et al 2000) and have begun forming immature synapses onto the tectal neurons-and 45. During this time in development, both synaptic drive and intrinsic excitability tended to increase (Pratt and Aizenman 2007).…”

Homeostatic Regulation of Intrinsic Excitability and Synaptic Transmission in a Developing Visual Circuit

“…Specifically, we focus on three periods of early development of the retinotectal circuit: stage 42/43, stages 44 -46, and stage 49 (see Materials and Methods for timing of stages). After RGC axons first reach their target tectum around developmental stage 39 (Holt, 1989;Dingwell et al, 2000), they begin to make functional synapses and convey visual information (stage 42/43). This is followed by a dynamic phase of synaptic formation and loss, as tectal cell dendrites grow and become more complex, and RGC axon terminals are highly motile (stages 44 -46) (Cline et al, 1997).…”

Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids

“…In addition, while RGC axons were capable of growth into varied assembloid models, RGCs extended longer axons into prosencephalic brain organoids, yet the number of RGC axons was increased within thalamic organoids. These observations suggest that the environment within thalamic organoids provides more suitable cues for RGCs to explore rather than quickly pass through, reminiscent of topographic mapping in the tectum when RGCs begin to enter the LGN and slow their growth and increase branching in the stages prior to refinement ( Dingwell et al., 2000 ; Godement and Mason, 1993 ). Overall, these results will provide a foundation for future studies of human RGC axonal outgrowth and the environmental cues that guide this pathfinding.…”