Generating X

Abstract

At the optic chiasm, axons from either eye meet and decide whether to cross contralaterally or turn back ipsilaterally. Here, the guidance ligand Slit and its receptor Robo control not whether axons cross (as in other midline decisions), but where the chiasm forms. Whether axons cross is instead controlled by the transcription factor Zic2 and the guidance receptor EphB1, as shown by two papers in the current issues of Neuron and Cell (Herrera et al. and Williams et al.). Surprisingly, this mechanism is conserved evolutionarily from frogs to mammals.

Slit2 is necessary for optic axon organization in the zebrafish ventral midline

“…As it has been indicated by previous research, the decision to cross the midline is probably one of the most delicately regulated steps in RGC axon growth to their targets (Herrera et al, 2019;Rasband et al, 2003). Our time-lapse imaging analyses indicate that, in the absence of Slit2, retinal axons presented larger and more complex growth cones, and frequently made mistakes, especially when approaching the midline, similar to what was reported for the astray/robo2 mutant (Hutson and Chien, 2002).…”

“…One of them is cell adhesion, either between axons or with surrounding glial cells (see for example Bruce et al, 2017;Masai et al, 2003). The other one is given by repulsive interactions between axons and surrounding tissues (surround repulsion), which can also favor fasciculation by channeling axons into a common path, a mechanism that has been suggested for Slits (Rasband et al, 2003). Functions in fasciculation have previously been attributed to the Slit-Robo signaling pathway in Drosophila (Bhat, 2017) and to Slit2 acting through Robo1 and Robo2 in mice (Jaworski and Tessier-Lavigne, 2012).…”

“…Since these extracellular matrix molecules are known to bind Slits with high affinity, it has been suggested that the axon sorting alterations occur as a result of a disruption in the extracellular distribution of Slit2 (Wright et al, 2012). On the other hand, it is important to note that a parallelism between mice and zebrafish might result difficult to establish regarding axon guidance at the optic chiasm, given some essential differences: a-in mice, which possess some degree of binocular vision, most RGC axons cross contralaterally and some take an ipsilateral turn at the optic chiasm (Jeffery and Erskine, 2005), while zebrafish lack binocular vision and present only contralateral axon crossing; b-a different set of Slit proteins are co-expressed in these regions: Slit1/2 in mice and Slit2/3 in zebrafish (Rasband et al, 2003).…”

Retinal axon guidance: novel mechanisms for steering

“…Experiments on RGC axons have significantly improved our understanding in all of these areas. Other exciting advances in the field of retinal axon guidance are the elucidation of the way that axons choose to grow ipsilaterally or contralaterally at the optic chiasm ([4–7] and Mason and colleagues, this issue), how they stay confined to the optic pathway [8–11] and the mechanisms that underlie topographic mapping along the dorso-ventral (medio-lateral) dimension in the tectum [12,13]. The current review focuses primarily on new concepts and molecular mechanisms that are involved in axon guidance, such as crosstalk modulation, age-related intrinsic changes, local translation and termination of signaling through degradation and endocytosis.…”

Retinal ganglion cell interactions shape the developing mammalian visual system

“…3 C), at which a portion cross over (contralateral or c-RGC) and the remainder maintain their trajectory (ipsilateral or i-RGC). These contra- and ipsilateral-projecting pathways are the basis of binocular vision ( Rasband et al, 2003 ) in vertebrates. The optic chiasm, where RGC axons cross, is a location where axon guidance molecules are interpreted to be repulsive or attractive (reviewed by Erskine and Herrera, 2007 ; Rasband et al, 2003 ).…”