Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

Wong, Yu Hui; Lu, Ai Chu; Wang, Yu Chiuan; Cheng, Hsu-Chen; Chang, Chau‐Lyan; Chen, Po Hao; Yu, Jenn Yah; Fann, Ming Ji

doi:10.1523/jneurosci.0473-10.2010

Cited by 51 publications

(43 citation statements)

References 32 publications

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“…In the chick spinal cord, Prtg expression is inversely correlated with Ascl1 expression, similar to what we have found in the retina (48). Prtg is a member of the DCC/Neogenin family (49,50) and contains four Ig and five fibronectin III domains in the extracellular domain.…”

Section: Discussionsupporting

confidence: 85%

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Torre

Georgi²,

Reh

2013

Proc. Natl. Acad. Sci. U.S.A.

198

189

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Most regions of the vertebrate central nervous system develop by the sequential addition of different classes of neurons and glia. This phenomenon has been best characterized in laminated structures like the retina and the cerebral cortex, in which the progenitor cells in these structures are thought to change in their competence as development proceeds to generate different types of neurons in a stereotypic sequence that is conserved across vertebrates. We previously reported that conditional deletion of Dicer prevents the change in competence of progenitors to generate later-born cell types, suggesting that specific microRNAs (miRNAs) are required for this developmental transition. In this report, we now show that three miRNAs, let-7, miR-125, and miR-9, are key regulators of the early to late developmental transition in retinal progenitors: (i) members of these three miRNA families increase over the relevant developmental period in normal retinal progenitors; (ii) inhibiting the function of these miRNAs produces changes in retinal development similar to Dicer CKO; (iii) overexpression of members of these three miRNA families in Dicer-CKO retinas can rescue the phenotype, allowing their progression to late progenitors; (iv) overexpression of these miRNAs can accelerate normal retinal development; (v) microarray and computational analyses of Dicer-CKO retinal cells identified two potential targets of the late-progenitor miRNAs: Protogenin (Prtg) and Lin28b; and (vi) overexpression of either Lin28 or Prtg can maintain the early progenitor state. Together, these data demonstrate that a conserved miRNA pathway controls a key step in the progression of temporal identity in retinal progenitors.heterochronic | progenitor competence

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Section: Discussionsupporting

confidence: 85%

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Torre

Georgi²,

Reh

2013

Proc. Natl. Acad. Sci. U.S.A.

198

189

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“…Finally, it will be interesting to determine if UPR-dependent regulation of secretory chaperones such as ERdj3 have non-proteostasis roles in regulating organismal physiology. For example, secreted ERdj3 is involved in multiple signaling pathways during development [49, 50]. This suggests that UPR-dependent regulation of ERdj3 secretion could function as an extracellular signal to coordinate organismal physiology during ER stress through mechanisms such as the non-cell autonomous UPR signaling observed in C. elegans [51].…”

Section: Influencing Downstream Secretory Proteostasis Environments Tmentioning

confidence: 99%

Regulating Secretory Proteostasis through the Unfolded Protein Response: From Function to Therapy

Plate

Wiseman

2017

Trends in Cell Biology

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SUMMARY Imbalances in secretory proteostasis induced by genetic, environmental or aging related insults are pathologically associated with etiologically diverse protein misfolding diseases. To protect the secretory proteome from these insults, organisms evolved stress-responsive signaling pathways that regulate the composition and activity of biologic pathways involved in secretory proteostasis maintenance. The most prominent of these is the endoplasmic reticulum (ER) Unfolded Protein Response (UPR), which functions to regulate ER proteostasis in response to ER stress. While the signaling mechanisms involved in UPR activation are well-defined, the impact of UPR activation on secretory proteostasis is only becoming clear. Here, we highlight recent reports defining how activation of select UPR signaling pathways influences proteostasis within the ER and downstream secretory environments. Furthermore, we describe recent evidence that highlights the therapeutic potential for targeting UPR signaling pathways to correct pathologic disruption in secretory proteostasis associated with diverse types of protein misfolding diseases.

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“…To detect PcxGFP and -tubulin, anti-GFP (1:1000) and anti--tubulin antibodies (E7, 1:2000) (Wong et al, 2010) were used, respectively.…”

Section: Western Blotting Analysis Of Pcxgfpmentioning

confidence: 99%

Deficient Notch signaling associated with neurogenicpecanexis compensated for by the unfolded protein response inDrosophila

et al. 2012

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SUMMARYThe Notch (N) signaling machinery is evolutionarily conserved and regulates a broad spectrum of cell-specification events, through local cell-cell communication. pecanex (pcx) encodes a multi-pass transmembrane protein of unknown function, widely found from Drosophila to humans. The zygotic and maternal loss of pcx in Drosophila causes a neurogenic phenotype (hyperplasia of the embryonic nervous system), suggesting that pcx might be involved in N signaling. Here, we established that Pcx is a component of the N-signaling pathway. Pcx was required upstream of the membrane-tethered and the nuclear forms of activated N, probably in N signal-receiving cells, suggesting that pcx is required prior to or during the activation of N. pcx overexpression revealed that Pcx resides in the endoplasmic reticulum (ER). Disruption of pcx function resulted in enlargement of the ER that was not attributable to the reduced N signaling activity. In addition, hyper-induction of the unfolded protein response (UPR) by the expression of activated Xbp1 or dominant-negative Heat shock protein cognate 3 suppressed the neurogenic phenotype and ER enlargement caused by the absence of pcx. A similar suppression of these phenotypes was induced by overexpression of O-fucosyltransferase 1, an N-specific chaperone. Taking these results together, we speculate that the reduction in N signaling in embryos lacking pcx function might be attributable to defective ER functions, which are compensated for by upregulation of the UPR and possibly by enhancement of N folding. Our results indicate that the ER plays a previously unrecognized role in N signaling and that this ER function depends on pcx activity.

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Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

Cited by 51 publications

References 32 publications

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Regulating Secretory Proteostasis through the Unfolded Protein Response: From Function to Therapy

Deficient Notch signaling associated with neurogenicpecanexis compensated for by the unfolded protein response inDrosophila

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