Guide cells help navigate axon regeneration

doi:10.1126/science.abc8066

GSTDTAP > 气候变化

DOI	10.1126/science.abc8066
	Guide cells help navigate axon regeneration
	Rachel Roberts-Galbraith
	2020-06-26
发表期刊	Science
出版年	2020
英文摘要	During embryonic development, neurons project nascent axons that navigate through space to find their targets. Axonal-growth paths forged by these pioneer axons depend on chemical and physical cues from cells that can include guidepost cells, which directly interact with nascent axons and induce them to grow, stop, or turn ([ 1 ][1]). A series of guidepost cells can serve as “stepping stones” to organize the complex growth of an axon in space ([ 2 ][2], [ 3 ][3]). Although guidepost cells direct axon formation during embryonic development in diverse model organisms, their existence often is transient. Thus, it was unclear whether guidepost-like cells promote axon regeneration and whether regenerative guidepost cells are constitutive or induced by injury. On page 1447 of this issue, Scimone et al. ([ 4 ][4]) pinpoint regenerative guidepost-like cells in the visual system of freshwater flatworms called planarians. Planarians are well known for their ability to regenerate diverse cell types in predictable patterns even in the face of severe injuries or amputations ([ 5 ][5]). One of the most recognizable features of the planarian body is a pair of crossed eyespots, which consist of pigment cells that form optic cups and photoreceptor neurons that nestle their photosensitive elements within the pigmented cups ([ 6 ][6]). From the eyespots, planarian photoreceptor neurons project axons through space to connect to the cephalic ganglia (a bilobed, horseshoe-shaped brain). The eyespots are positioned dorsally and the brain ventrally in the planarian head. Thus, photoreceptor axons must project ventrally and also turn to make either contralateral or ipsilateral contacts ([ 7 ][7]). This highly predictable structure made planarian photoreceptor neurons ideal for the identification of cellular guideposts that direct axon organization during regeneration. Scimone et al. thus began their search for regenerative guidepost-like cells that shape the planarian visual system (see the figure). By investigating notum gene–expressing cells ( notum +) that are associated with photoreceptor neurons, the authors discovered three distinct cell types specifically positioned at axonal decision points ([ 4 ][4]). The authors first identified clusters of muscle cells near the eyespots, called NMEs ( notum + muscle cells near the eye), and proposed that these cells promote the bundling of axons as they exit the posterior of the eyespot. A second group of muscle cells called NMCs ( notum + muscle cells at the choice point) were found near decision points for axons as they diverged to project toward ipsilateral or contralateral contact sites. The third cluster of guidepost-like cells were neurons called NBCs ( notum + brain cells), which localized medially and worked either alone or with other medial neurons to promote midline crossing of photoreceptor axons at the optic chiasm. ![Figure][8] Guidepost-like cells govern planarian regeneration Three specialized cell types direct the growth and positioning of nascent axons during regeneration of the visual system. GRAPHIC: C. BICKEL/ SCIENCE A combination of physical and molecular manipulations revealed that NMEs, NMCs, and NBCs serve as guidepost-like cells during regeneration to assist photoreceptor axons toward their final arrangement. This demonstrates that highly regenerative organisms like planarians can use constitutive guidepost-like cells to promote a lifelong capacity for neuronal replacement and axon guidance. The new research also addresses long-standing questions about the ubiquity of guidepost cells across the animal kingdom. One surprise in the new study is the identity of the guidepost-like cells. Whereas guideposts are often neurons, glia, or epithelial cells ([ 1 ][1]), Scimone et al. unexpectedly determined that two of the three guidepost-like populations in the planarian visual system express markers of muscle identity. Although previous studies revealed a global role for muscles in body axis patterning ([ 8 ][9]), the current work illustrates that planarian muscle cells also act locally to shape individual organ systems and even to direct the physical arrangement of single cells. The third population of planarian guidepost-like cells, NBCs, were neurons. Although less surprising, this finding fits into an emerging theme of planarian neurons influencing brain regeneration in a multitude of ways, from patterning to fate choice. notum + neurons at the anterior-most end of the planarian brain influence brain scaling ([ 9 ][10]), and a population of medial neurons produces Hedgehog ligand to promote neurogenesis ([ 10 ][11]). Scimone et al. also built on the prior identification of arrowhead as a key transcription factor–encoding gene that is expressed in medial neurons (including NBCs) and influences medial patterning of photoreceptors and the anterior commissure, the largest connection between halves of the planarian brain ([ 11 ][12]). It remains unknown whether guidepost-like cells organize the positioning of other planarian neuronal structures during regeneration (for example, axons that run along the ventral nerve cords, axons that project into the planarian pharynx, or neural processes that bundle together to form sensory structures) ([ 6 ][6]). Planarian guidepost-like cells might also regulate other aspects of neuronal cell behavior during regeneration, including cell migration or synapse formation. After amputation, planarian guidepost-like cells must themselves be regenerated and positioned properly. Scimone et al. determined that these cells regenerate independently of photoreceptor neurons; they discovered factors (intrinsic and extrinsic) that regulate regeneration of guidepost-like cells and ensure their proper arrangement in space. However, the precise mechanisms that direct regeneration of each cell type remain unknown. The new work raises the intriguing possibility that human neural regeneration might be improved by mimicking the guideposts that direct vertebrate axon formation during development. Human neurons in the brain and spinal cord usually fail to regenerate axons after injury. However, introducing cellular or molecular “stepping stones” along a desired axonal path might coax axons toward better regrowth. Current and future research investigating this theme—in fields ranging from bioengineering to basic developmental biology—might reveal the extent to which cues or matrices meant to mimic guidepost-like cells can improve axon guidance for various populations of adult human neurons ([ 12 ][13]). 1. [↵][14]1. D. L. Chao, 2. L. Ma, 3. K. Shen , Nat. Rev. Neurosci. 10, 262 (2009). [OpenUrl][15][CrossRef][16][PubMed][17][Web of Science][18] 2. [↵][19]1. C. M. Bate , Nature 260, 54 (1976). [OpenUrl][20][CrossRef][21][PubMed][22] 3. [↵][23]1. J. Palka, 2. K. E. Whitlock, 3. M. A. Murray , Curr. 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领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/278203
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Rachel Roberts-Galbraith. Guide cells help navigate axon regeneration[J]. Science,2020.
APA	Rachel Roberts-Galbraith.(2020).Guide cells help navigate axon regeneration.Science.
MLA	Rachel Roberts-Galbraith."Guide cells help navigate axon regeneration".Science (2020).