Abstract
Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues. Computational modeling suggests that topographic accuracy and adaptability, though seemingly incompatible, could be reconciled by a novel mechanism of coupled adaptation of signaling channels. Experimentally, we find such 'co-adaptation' in retinal growth cones specifically for ephrin-A/EphA signaling. Co-adaptation involves trafficking of unliganded sensors between the surface membrane and recycling endosomes, and is presumably triggered by changes in the lipid composition of membrane microdomains. We propose that co-adaptative desensitization eventually relies on guidance sensor translocation into cis-signaling endosomes to outbalance repulsive trans-signaling.
Highlights
The dazzling diversity of functions of the nervous system are brought about by neural networks of definite connectivity, most of which arise during ontogenesis through targeted outgrowth of axons
Using SNAP-tagged ephrin-A5 to label sensor surface populations, pharmacological inhibition, and co-localization studies with Rab11, we show that coadaptation on the cellular level involves trafficking of the guidance sensors between the growth cones (GCs) membrane and the recycling endosome
Retinal GCs adapt towards topographic EphA forward and ephrin-A reverse signals
Summary
The dazzling diversity of functions of the nervous system are brought about by neural networks of definite connectivity, most of which arise during ontogenesis through targeted outgrowth of axons This is accomplished by growth cones (GCs) at the tips of growing axons (Lowery and Van Vactor, 2009; Vitriol and Zheng, 2012), which sense genetically encoded chemotactic guidance cues (Dickson, 2002; Kolodkin and Tessier-Lavigne, 2011). A well-studied example is the development of the retinotectal projection (Figure 1), which, in non-mammalian vertebrates, connects the retinal ganglion cells (RGCs) of the eye with the midbrain’s optic tectum in a topographic, i.e., neighborhood-preserving manner (Feldheim and O’Leary, 2010; Lemke and Reber, 2005; Weth et al, 2014) Research on this two-dimensional mapping has mainly focused on the anterior-posterior axis, whereby the temporal retina is projected onto the anterior tectum and the nasal retina onto the posterior tectum.
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