Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons

Wehner, Amanda Beth; Abdesselem, Houari; Dickendesher, Travis L.; Imai, Fumiyasu; Yoshida, Yutaka; Giger, Roman J.; Pierchala, Brian A.

doi:10.1242/jcs.191593

Cited by 6 publications

(13 citation statements)

References 36 publications

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“…The lens ablation itself would stimulate the increase of periocular nerve fascicles, and caffeine administration in absence of the lens did recover the NF + corneal innervation compared with the caffeine only treated group (Figure ), suggesting that lens‐derived SemaA–Nrp1 signaling plays a role on maintaining the corneal innervation of normal eye development. Likewise, Wehner et al () also reported that Sema3A was implicated in regulating developmental sympathetic neuron death.…”

Section: Discussionmentioning

confidence: 90%

“…Sema3A-Nrp1 signaling in the lens (Supporting Information Figure S3). Thus, we consider that more likely the second possibility is a more realistic one because ROS can also negatively Likewise, Wehner et al (2016) (Oppenheim, 1991). Therefore, it is conceivable that the detrimental environment like caffeine administration might actively induce the developing neuron apoptosis at the early developmental stage.…”

Section: Knockdown Of Sema3a Expression Alters Sh-sy5y Cell Survivamentioning

confidence: 99%

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Cell survival controlled by lens‐derived Sema3A–Nrp1 is vital on caffeine‐suppressed corneal innervation during chick organogenesis

Wang

Jiang

Tan

et al. 2018

Journal Cellular Physiology

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In this study, we investigated the effect of caffeine overexposure on corneal innervation in the early chicken embryo. Caffeine administration restricted corneal innervation by affecting trigeminal nerve development. Immunohistochemistry for phospho‐Histone3 (pHIS3) and C‐caspase3 revealed that cell survival was repressed by caffeine administration. Whole‐mount in situ hybridization against semaphorin 3A (Sema3A) and neuropilin‐1 (Nrp1) showed that both caffeine and 2,2′‐azobis(2‐methylpropionamidine) dihydrochloride (AAPH, a free radical generator) administration upregulates the expression of both Sema3A and Nrp1. Next, we demonstrated that lens ablation in the developing chicken embryos significantly affected NF‐labeled periocular nerve fascicles and innervation to the central eye region. Subsequently, we used a neuroblastoma cell line to investigate in vitro whether or not Sema3A–Nrp1 signaling exerts a key role on the caffeine‐suppressed neuron survival. Knocking‐down Sema3A through transfection with Sema3A‐siRNA dramatically decreased the responsiveness of cells to caffeine administration, as well as cell apoptosis. We suggest that Sema3A–Nrp1 signaling regulates Trp53 and Cdkn1a through Slit2–Robo1 and Ephb2. Taken together, we speculate here that caffeine‐enhanced reactive oxygen species upregulates Sema3A–Nrp1 expression in the lens and periocular tissues, resulting in corneal cell apoptosis, accompanied by its chemorepellent role on the invasion of the developing cornea by trigeminal sensory fibers.

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Section: Discussionmentioning

confidence: 90%

Section: Knockdown Of Sema3a Expression Alters Sh-sy5y Cell Survivamentioning

confidence: 99%

Cell survival controlled by lens‐derived Sema3A–Nrp1 is vital on caffeine‐suppressed corneal innervation during chick organogenesis

Wang

Jiang

Tan

et al. 2018

Journal Cellular Physiology

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“…This apparent discrepancy could be due to the fact that whole‐body Nrp1 deficiency in both humans and mice alters the projection of the vomeronasal and terminal nerve fibers in the frontonasal region and thus disrupts the migration of GnRH neurons into the brain (Hanchate et al , ; Marcos et al , ), whereas the impairment of Nrp1 signaling selectively in GnRH neurons increases their survival and therefore their numbers, accelerates their migration, and potentially alters their integration into the hypothalamic network controlling their activity after birth. It has been shown that Nrp1 signaling, besides playing a decisive role in neuronal guidance and axonal growth (Gu et al , ; Imai et al , ), also induces programmed cell death in neurons during development, both in vitro (Bagnard et al , ) and in vivo (Wehner et al , ). In agreement with this proapoptotic role of Nrp1 signaling, but in contrast to previously reported findings by others in whole‐body Nrp1 ‐null mice (Cariboni et al , 2011a), our results demonstrate that selectively knocking out Nrp1 in GnRH neurons markedly increases their numbers during embryogenesis.…”

Section: Discussionmentioning

confidence: 99%

Neuropilin‐1 expression in GnRH neurons regulates prepubertal weight gain and sexual attraction

et al. 2020

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Hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH), the "master molecule" regulating reproduction and fertility, migrate from their birthplace in the nose to their destination using a system of guidance cues, which include the semaphorins and their receptors, the neuropilins and plexins, among others. Here, we show that selectively deleting neuropilin-1 in new GnRH neurons enhances their survival and migration, resulting in excess neurons in the hypothalamus and in their unusual accumulation in the accessory olfactory bulb, as well as an acceleration of mature patterns of activity. In female mice, these alterations result in early prepubertal weight gain, premature attraction to male odors, and precocious puberty. Our findings suggest that rather than being influenced by peripheral energy state, GnRH neurons themselves, through neuropilin-semaphorin signaling, might engineer the timing of puberty by regulating peripheral adiposity and behavioral switches, thus acting as a bridge between the reproductive and metabolic axes.

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“…Axon guidance cues have also been described to continue to function after target innervation. For example, repulsive axon guidance cues like semaphorin 3a (sema3a), Slit‐Robo and Eph‐Ephrins have been associated with cell death in multiple cell types after target innervation (Dickinson, Fegan, Ren, Hillier, & Duncan, 2011; Gagliardini & Fankhauser, 1999; Kellermeyer, Heydman, Mastick, & Kidd, 2018; H. Lee, Park, Kang, & Park, 2015; Wehner et al, 2016). Presumably, this is a way in which neurons innervating incorrect targets can be rapidly removed from a pool competing for neurotrophic factors derived from correct targets.…”

Section: Overview Of Progressive and Regressive Cues From Target Tissuesmentioning

confidence: 99%

Long‐distance regressive signaling in neural development and disease

Pathak

Clark

Bronfman

et al. 2020

WIREs Developmental Biology

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Nervous system development proceeds via well‐orchestrated processes involving a balance between progressive and regressive events including stabilization or elimination of axons, synapses, and even entire neurons. These progressive and regressive events are driven by functionally antagonistic signaling pathways with the dominant pathway eventually determining whether a neural element is retained or removed. Many of these developmental sculpting events are triggered by final target innervation necessitating a long‐distance mode of communication. While long‐distance progressive signaling has been well characterized, particularly for neurotrophic factors, there remains relatively little known about how regressive events are triggered from a distance. Here we discuss the emergent phenomenon of long‐distance regressive signaling pathways. In particular, we will cover (a) progressive and regressive cues known to be employed after target innervation, (b) the mechanisms of long‐distance signaling from an endosomal platform, (c) recent evidence that long‐distance regressive cues emanate from platforms like death receptors or repulsive axon guidance receptors, and (d) evidence that these pathways are exploited in pathological scenarios. This article is categorized under: Nervous System Development > Vertebrates: General Principles Signaling Pathways > Global Signaling Mechanisms Establishment of Spatial and Temporal Patterns > Cytoplasmic Localization

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Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons

Cited by 6 publications

References 36 publications

Cell survival controlled by lens‐derived Sema3A–Nrp1 is vital on caffeine‐suppressed corneal innervation during chick organogenesis

Cell survival controlled by lens‐derived Sema3A–Nrp1 is vital on caffeine‐suppressed corneal innervation during chick organogenesis

Neuropilin‐1 expression in GnRH neurons regulates prepubertal weight gain and sexual attraction

Long‐distance regressive signaling in neural development and disease

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