Neural crest Notch/Rbpj signaling regulates olfactory gliogenesis and neuronal migration

Miller, Sophie R.; Benito, Cristina; Mirsky, Rhona; Jessen, Kristján R.; Baker, Clare V. H.

doi:10.1002/dvg.23215

Cited by 10 publications

(12 citation statements)

References 86 publications

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“…Further, these observations suggest that the near complete absence of Sox10 ϩ OECs in the nasal mucosa of Gli3 Xt/Xt mutants is not a only the result of defective vomeronasal neurogenesis (Fig. 8O) (Miller et al, 2018;Rich et al, 2018), but likely secondary to neural crest defects (Matera et al, 2008). In support of this conjecture, we observed that Gli3 Xt/WT /Ascl-1 ϩ/Ϫ double mutants were indistinguishable from Gli3 Xt/WT single mutants (data not shown).…”

Section: Ascl-1 Loss-of-function Compromises Vno and Gnrh-1 Neurogenementioning

confidence: 53%

“…Moreover, Gli3 Xt/WT /Ascl-1 ϩ/Ϫ double mutants did not have exacerbated phenotypes compared with Gli3 Xt/WT suggesting that the effects seen in both Ascl-1 null and Gli3 Xt/Xt are independent of each other and not additive (data not shown). We conclude that the near complete absence of OECs in the nasal mucosa of Gli3 Xt/Xt mutants is not secondary to the decreased number of vomeronasal fibers (Miller et al, 2018).…”

Section: Discussionmentioning

confidence: 73%

“…OECs promote normal GnRH-1 neuronal migration from the nasal area to the brain (Barraud et al, 2013;Geller et al, 2013;Pingault et al, 2013). OECs arise from the neural crest precursors (Barraud et al, 2010;Forni et al, 2011b;Miller et al, 2016Miller et al, , 2018Rich et al, 2018). By analyzing GnRH-1ns migration in Gli3 Xt/Xt mutants, we found that most GnRH-1 cells were unable to migrate far from the VNO and formed large clumps of cells on tangled fibers of the putative TN.…”

Section: Discussionmentioning

confidence: 90%

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Gli3 Regulates Vomeronasal Neurogenesis, Olfactory Ensheathing Cell Formation, and GnRH-1 Neuronal Migration

et al. 2019

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During mammalian development, gonadotropin-releasing-hormone-1 neurons (GnRH-1ns) migrate from the developing vomeronasal organ (VNO) into the brain asserting control of pubertal onset and fertility. Recent data suggest that correct development of the olfactory ensheathing cells (OEC) is imperative for normal GnRH-1 neuronal migration. However, the full ensemble of molecular pathways that regulate OEC development remains to be fully deciphered. Loss-of-function of the transcription factor Gli3 is known to disrupt olfactory development, however, if Gli3 plays a role in GnRH-1 neuronal development is unclear. By analyzing Gli3 extra-toe mutants (Gli3 Xt/Xt), we found that Gli3 loss-of-function compromises the onset of achaete-scute family bHLH transcription factor 1 (Ascl-1) ϩ vomeronasal progenitors and the formation of OEC in the nasal mucosa. Surprisingly, GnRH-1 neurogenesis was intact in Gli3 Xt/Xt mice but they displayed significant defects in GnRH-1 neuronal migration. In contrast, Ascl-1 null mutants showed reduced neurogenesis for both vomeronasal and GnRH-1ns but less severe defects in OEC development. These observations suggest that Gli3 is critical for OEC development in the nasal mucosa and subsequent GnRH-1 neuronal migration. However, the nonoverlapping phenotypes between Ascl-1 and Gli3 mutants indicate that Ascl-1, while crucial for GnRH-1 neurogenesis, is not required for normal OEC development. Because Kallmann syndrome (KS) is characterized by abnormal GnRH-1ns migration, we examined whole-exome sequencing data from KS subjects. We identified and validated a GLI3 loss-of-function variant in a KS individual. These findings provide new insights into GnRH-1 and OECs development and demonstrate that human GLI3 mutations contribute to KS etiology.

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Section: Ascl-1 Loss-of-function Compromises Vno and Gnrh-1 Neurogenementioning

confidence: 53%

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 90%

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Gli3 Regulates Vomeronasal Neurogenesis, Olfactory Ensheathing Cell Formation, and GnRH-1 Neuronal Migration

et al. 2019

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“…During development, Notch receptors can regulate gross neuronal morphology and fine synaptic architecture through both canonical and non-canonical signaling in diverse species. This includes regulation of neuronal migration [ 144 , 145 , 146 , 147 ], neurite outgrowth and morphogenesis [ 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 ], axon guidance and targeting [ 159 , 160 , 161 , 162 , 163 , 164 ], dendrite morphogenesis [ 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 ], synaptogenesis [ 173 , 174 ], and synaptic growth [ 121 , 175 ]. Hence, one may consider that Notch signaling may regulate neuronal and synaptic physiology by fine-tuning cellular mechanisms that lead to structural alterations in the post-developmental brain.…”

Section: Mechanisms By Which Post-developmental Notch Signaling Rementioning

confidence: 99%

Post-Developmental Roles of Notch Signaling in the Nervous System

2020

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Since its discovery in Drosophila, the Notch signaling pathway has been studied in numerous developmental contexts in diverse multicellular organisms. The role of Notch signaling in nervous system development has been extensively investigated by numerous scientists, partially because many of the core Notch signaling components were initially identified through their dramatic ‘neurogenic’ phenotype of developing fruit fly embryos. Components of the Notch signaling pathway continue to be expressed in mature neurons and glia cells, which is suggestive of a role in the post-developmental nervous system. The Notch pathway has been, so far, implicated in learning and memory, social behavior, addiction, and other complex behaviors using genetic model organisms including Drosophila and mice. Additionally, Notch signaling has been shown to play a modulatory role in several neurodegenerative disease model animals and in mediating neural toxicity of several environmental factors. In this paper, we summarize the knowledge pertaining to the post-developmental roles of Notch signaling in the nervous system with a focus on discoveries made using the fruit fly as a model system as well as relevant studies in C elegans, mouse, rat, and cellular models. Since components of this pathway have been implicated in the pathogenesis of numerous psychiatric and neurodegenerative disorders in human, understanding the role of Notch signaling in the mature brain using model organisms will likely provide novel insights into the mechanisms underlying these diseases.

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“…The initiating molecular events of SCLC are believed to be inactivation of TP53 and RB1, which mainly occurs in Kulchitsky cells in the respiratory epithelium, although many other genes and signaling pathways are disrupted, especially Notch signaling [114]. Notch signaling play various roles during neural crest development, especially in neurons differentiation [115,116]. Interestingly, TAMs are probably involved in SCLC progression through STAT3 activation and TAM-derived IL-6 can be one of molecules related to STAT3 activation in SCLC cells [117].…”

Section: Tumors Of Not Established Nc Originmentioning

confidence: 99%

Innate and Adaptive Immunity Linked to Recognition of Antigens Shared by Neural Crest-Derived Tumors

Donato

Presta

Arcidiacono

et al. 2020

Cancers

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In the adult, many embryologic processes can be co-opted by during cancer progression. The mechanisms of divisions, migration, and the ability to escape immunity recognition linked to specific embryo antigens are also expressed by malignant cells. In particular, cells derived from neural crests (NC) contribute to the development of multiple cell types including melanocytes, craniofacial cartilage, glia, neurons, peripheral and enteric nervous systems, and the adrenal medulla. This plastic performance is due to an accurate program of gene expression orchestrated with cellular/extracellular signals finalized to regulate long-distance migration, proliferation, differentiation, apoptosis, and survival. During neurulation, prior to initiating their migration, NC cells must undergo an epithelial–mesenchymal transition (EMT) in which they alter their actin cytoskeleton, lose their cell–cell junctions, apicobasal polarity, and acquire a motile phenotype. Similarly, during the development of the tumors derived from neural crests, comprising a heterogeneous group of neoplasms (Neural crest-derived tumors (NCDTs)), a group of genes responsible for the EMT pathway is activated. Here, retracing the molecular pathways performed by pluripotent cells at the boundary between neural and non-neural ectoderm in relation to the natural history of NCDT, points of contact or interposition are highlighted to better explain the intricate interplay between cancer cells and the innate and adaptive immune response.

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Neural crest Notch/Rbpj signaling regulates olfactory gliogenesis and neuronal migration

Cited by 10 publications

References 86 publications

Gli3 Regulates Vomeronasal Neurogenesis, Olfactory Ensheathing Cell Formation, and GnRH-1 Neuronal Migration

Gli3 Regulates Vomeronasal Neurogenesis, Olfactory Ensheathing Cell Formation, and GnRH-1 Neuronal Migration

Post-Developmental Roles of Notch Signaling in the Nervous System

Innate and Adaptive Immunity Linked to Recognition of Antigens Shared by Neural Crest-Derived Tumors

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