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Guide Cells Help Navigate Axon Regeneration Rachel Roberts-Galbraith

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Guide Cells Help Navigate Axon Regeneration Rachel Roberts-Galbraith INSIGHTS | PERSPECTIVES ulatory and protective processes is in place to underpowered state is metabolically insuf- NEUROBIOLOGY minimize damage. The fastest regulators ac- ficient, whereas the overpowered state risks tivate within minutes and relax on a similar photoinhibition. The question then is whether time scale when light returns to normal (8), the inputs are arranged in such a way that the Guide cells help but these arguably still lag behind the fastest output spends most of its time at the optimal fluctuations in light intensity (9). state, thereby minimizing output noise. As well, light harvesting is not finely The input channels represent different navigate axon tuned in a molecular sense. Instead, the groups of light-absorbing pigments. As picture is one of robustness in the face such, they are each defined by the wave- of external conditions (10) and even ge- length and rate at which they absorb. If regeneration netic manipulation. An extreme example their intrinsic rates (determined by chemi- is found in the model plant Arabidopsis cal properties and stoichiometry) are as- R ebuilding the flatworm thaliana, from which LHCII is eliminated sumed to be identical, then the overall rate visual system after injury through genetic manipulation. In re- of absorption is determined solely by the sponse, an ersatz antenna is formed from intensity of available light at that wave- requires guidepost-like assemblies of the remaining minor light- length. Consider, for example, two limiting muscle cells harvesting proteins (11). Although these regimes. If the two channels are identical mutant plants may not thrive like their (i.e., a single channel), then antenna homo- wild-type counterparts, they are certainly geneity minimizes internal noise. However, By Rachel Roberts-Galbraith having a single absorbing species makes the system very sensitive to external noise. uring embryonic development, Downloaded from “…the evolutionary driving Conversely, if the two channels differ neurons project nascent axons that strongly in both wavelength and absorp- navigate through space to find their force behind the development tion rate, then internal noise dominates. targets. Axonal-growth paths forged of photosynthetic antennae Optimum output is generated in an inter- by these pioneer axons depend on mediate regime where the two inputs have chemical and physical cues from is not maximization of efficiency similar wavelengths but different absorp- Dcells that can include guidepost cells, http://science.sciencemag.org/ tion rates. This is achieved by locating the which directly interact with nascent axons but the cancellation of noise. ” pair in a region of the spectrum of avail- and induce them to grow, stop, or turn able light that has the steepest gradient. (1). A series of guidepost cells can serve as photosynthetically competent. If there is With only this consideration in mind, Arp “stepping stones” to organize the complex some universal organizational principle et al. predicted, with a high degree of accu- growth of an axon in space (2, 3). Although behind light harvesting, it does not appear racy, the absorption profile of green plants, guidepost cells direct axon formation dur- to lie in the molecular detail. purple bacteria, and green sulfur bacteria. ing embryonic development in diverse Arp et al. have taken a new approach to in- The finding of Arp et al. is important be- model organisms, their existence often is vestigating the question of universal organi- cause it suggests that the evolutionary driv- transient. Thus, it was unclear whether zation. By applying network theory, they have ing force behind the development of pho- guidepost-like cells promote axon regen- determined the most basic organizational tosynthetic antennae is not maximization eration and whether regenerative guide- on July 9, 2020 requirements necessary for a light-harvesting of efficiency but the cancellation of noise. post cells are constitutive or induced by system to function optimally. The authors Moreover, the finding indicates that to build injury. On page 1447 of this issue, Scimone used a very generalized model of the antenna such a system, one must start from the sim- et al. (4) pinpoint regenerative guidepost- as a network of interconnected sites that can ple requirements of two similar absorbing like cells in the visual system of freshwater represent individual pigment states within species that are tuned to the steepest region flatworms called planarians . delocalized multipigment states across the (not the strongest) of the spectrum of avail- Planarians are well known for their antenna. Energy enters this network from able light. Fine structural details are impor- ability to regenerate diverse cell types in one or more input channels that reflect light tant, but they come as refinements to this predictable patterns even in the face of absorption through different types of pig- simple underlying principle. j severe injuries or amputations (5). One of ments. Two input channels were chosen as a the most recognizable features of the pla- minimal model (see the figure), which is rea- REFERENCES AND NOTES narian body is a pair of crossed eyespots, 1. T. B. Arp et al., Science 368, 1490 (2020). sonably representative of several real antenna 2. G. D. Scholes et al., Nat. Chem. 3, 763 (2011). which consist of pigment cells that form systems, such as chlorophyll a and b in LHCII 3. R. Croce, H. van Amerongen, Nat. Chem. Biol. 10, 492 optic cups and photoreceptor neurons or bacteriochlorophyll c and e in the antenna (2014). that nestle their photosensitive elements of green sulfur bacteria (12). Absorbed en- 4. T. P. J. Krüger, R. van Grondelle, Physica B 480, 7 (2016). within the pigmented cups (6). From the ergy can take many different paths through 5. G. R. Engel et al., Nature 446, 782 (2007). eyespots, planarian photoreceptor neurons 6. D. M. Wilkins, N. S. Dattani, J. Chem. Theory Comput. 11, the antenna. However, all paths terminate 3411 (2015). project axons through space to connect to at a single output channel representing pho- 7. B. Kok, Biochim. Biophys. Acta 21, 234 (1956). the cephalic ganglia (a bilobed, horseshoe- toinduced charge separation. Such a system 8. A. V. Ruban, M. P. Johnson, C. D. P. Duffy, Biochim. shaped brain). The eyespots are positioned is subject to a high degree of input noise. Biophys. Acta Bioenerg. 1817, 167 (2012). dorsally and the brain ventrally in the 9. J. Kromdijk et al., Science 354, 857 (2016). External noise comes from rapid fluctuations 10. P. Malý, A. T. Gardiner, R. J. Cogdell, R. van Grondelle, planarian head. Thus, photoreceptor ax- in the incident radiation, whereas internal T. Mančal, Phys. Chem. Chem. Phys. 20, 4360 (2018). ons must project ventrally and also turn noise originates from the structural dynam- 11. A. V. Ruban et al., J. Biol. Chem. 281, 14981 (2006). to make either contralateral or ipsilateral ics of the antenna. This results in a noisy 12. C. M. Borrego et al. , Photosynth. Res. 60, 257 (1999). output that fluctuates between underpow- Department of Cellular Biology, University of Georgia, ered, optimal, and overpowered states. The 10.1126/science.abc8063 Athens, GA 30602, USA. Email: [email protected] 1428 26 JUNE 2020 • VOL 368 ISSUE 6498 sciencemag.org SCIENCE Published by AAAS contacts (7). This highly predictable struc- lifelong capacity for neuronal replacement It remains unknown whether guidepost- ture made planarian photoreceptor neu- and axon guidance. The new research also like cells organize the positioning of other rons ideal for the identification of cellular addresses long-standing questions about planarian neuronal structures during re- guideposts that direct axon organization the ubiquity of guidepost cells across the generation (for example, axons that run during regeneration. animal kingdom. along the ventral nerve cords, axons that Scimone et al. thus began their search One surprise in the new study is project into the planarian pharynx, or neu- for regenerative guidepost-like cells that the identity of the guidepost-like cells. ral processes that bundle together to form shape the planarian visual system (see the Whereas guideposts are often neurons, sensory structures) (6). P lanarian guide- figure). By investigating notum gene–ex- glia, or epithelial cells (1), Scimone et al. post-like cells might also regulate other pressing cells (notum+) that are associated unexpectedly determined that two of the aspects of neuronal cell behavior during with photoreceptor neurons, the authors three guidepost-like populations in the regeneration, including cell migration or discovered three distinct cell types specifi- planarian visual system express markers of synapse formation. cally positioned at axonal decision points muscle identity. Although previous studies After amputation, planarian guidepost- (4). The authors first identified clusters revealed a global role for muscles in body like cells must themselves be regenerated of muscle cells near the eyespots, called axis patterning (8), the current work illus- and positioned properly. Scimone et al. de- NMEs (notum+ muscle cells near the eye), trates that planarian muscle cells also act termined that these cells regenerate inde- and proposed that these cells promote the locally to shape individual organ systems pendently of photoreceptor neurons; they bundling of axons as they exit the posterior and even to direct the physical arrange- discovered factors (intrinsic and extrinsic) of the eyespot. A second group of muscle ment of single cells. that regulate regeneration of guidepost- like cells and ensure their proper arrange- ment in space. However, the precise mech- Downloaded from Guidepost-like cells govern planarian regeneration anisms that direct regeneration of each cell Three specialized cell types direct the growth and positioning of nascent axons during regeneration type remain unknown. of the visual system. The new work raises the intriguing possibility that human neural regenera- tion might be improved by mimicking Head Eyespot Regeneration the guideposts that direct vertebrate axon http://science.sciencemag.org/ Planarians are well known for their formation during development.
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