The Abelson tyrosine kinase regulates Notch endocytosis and signaling to maintain neuronal cell fate in<i>Drosophila</i>photoreceptors

Xiong, Wenjun; Morillo, Santiago A.; Rebay, Ilaria

doi:10.1242/dev.088799

Cited by 15 publications

(19 citation statements)

References 38 publications

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“…1I, K). This inconsistency might be ascribed to some factors induced by hypoxia that are involved in hypoxia-induced neurogenesis such as Notch 1 signaling [33][34][35]. Notch 1 is known to be crucial for the self-renewal and fate-decision of NSCs and promotes ischemia-induced neurogenesis in the hippocampus by cleaving Notch 1 and increasing the level of NICD (notch intracellular domain), the active form of Notch 1 that translocates to the nucleus and regulates transcription [36,37].…”

Section: Pfk-1 Reduces the Neuronal Differentiation Of Nscs After Hypmentioning

confidence: 99%

Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

et al. 2016

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Phosphofructokinase-1 (PFK-1), a major regulatory glycolytic enzyme, has been implicated in the functions of astrocytes and neurons. Here, we report that PFK-1 negatively regulates neurogenesis from neural stem cells (NSCs) by targeting pro-neural transcriptional factors. Using in vitro assays, we found that PFK-1 knockdown enhanced, and PFK-1 overexpression inhibited the neuronal differentiation of NSCs, which was consistent with the findings from NSCs subjected to 5 h of hypoxia. Meanwhile, the neurogenesis induced by PFK-1 knockdown was attributed to the increased proliferation of neural progenitors and the commitment of NSCs to the neuronal lineage. Similarly, in vivo knockdown of PFK-1 also increased neurogenesis in the dentate gyrus of the hippocampus. Finally, we demonstrated that the neurogenesis mediated by PFK-1 was likely achieved by targeting mammalian achaete-scute homologue-1 (Mash 1), neuronal differentiation factor (NeuroD), and sex-determining region Y (SRY)-related HMG box 2 (Sox2). All together, our results reveal PFK-1 as an important regulator of neurogenesis.

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Section: Pfk-1 Reduces the Neuronal Differentiation Of Nscs After Hypmentioning

confidence: 99%

Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

et al. 2016

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“…The results of the present study indicated that Past1 plays a role during eye development, which is known to be regulated by Notch [17, 19, 27, 40]. Interestingly, endocytosis of Notch seemed abnormal in early-mid pupal mutant eyes.…”

Section: Discussionmentioning

confidence: 61%

Past1 Modulates Drosophila Eye Development

et al. 2017

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Endocytosis is a multi-step process involving a large number of proteins, both general factors, such as clathrin and adaptor protein complexes, and unique proteins, which modulate specialized endocytic processes, like the EHD proteins. EHDs are a family of Eps15 Homology Domain containing proteins that consists of four mammalian homologs, one C. elegans, one Drosophila melanogaster and two plants orthologs. These membrane-associated proteins are involved in different steps of endocytic trafficking pathways. We have previously shown that the Drosophila EHD ortholog, PAST1, associates predominantly with the plasma membrane. Mutations in Past1 result in defects in endocytosis, male sterility, temperature sensitivity and premature death of the flies. Also, Past1 genetically interacts with Notch. In the present study, we investigated the role of PAST1 in the developing fly eye. In mutant flies lacking PAST1, abnormal differentiation of photoreceptors R1, R6 and R7 was evident, with partial penetrance. Likewise, five cone cells were present instead of four. Expression of transgenic PAST1 resulted in a dominant negative effect, with a phenotype similar to that of the deletion mutant, and appearance of additional inter-ommatidial pigment cells. Our results strongly suggest a role for PAST1 in differentiation of photoreceptors R1/R6/R7 and cone cells of the fly ommatidia.

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“…We examined Sce mutant R7s throughout larval and pupal development and found none that misexpressed Svp, nor did we observe Sce or Scm mutant R7s that displayed other R1/R6 characteristics, such as large rhabdomeres positioned at the periphery of the ommatidium or expression of the R1-R6-specific rhodopsin Rh1; [ 28 , 29 , 45 ]). While loss of the Abelson kinase was recently shown to cause R neurons to lose expression of the neuronal marker Elav and switch to a non-neuronal pigment cell fate [ 50 ], we found that Sce and Scm mutant R1/R6s and R7s maintain expression of Elav and the photoreceptor-specific protein Chaoptin (for example, Figure 1 B), indicating that their commitment to a neuronal fate is also independent of PcG gene function. We conclude that R7s use Sce and Scm to maintain repression of one but not all alternative binary fate choices.…”

Section: Discussionmentioning

confidence: 47%

Polycomb group genes are required to maintain a binary fate choice in the Drosophila eye

2015

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BackgroundIdentifying the mechanisms by which cells remain irreversibly committed to their fates is a critical step toward understanding and being able to manipulate development and homeostasis. Polycomb group (PcG) proteins are chromatin modifiers that maintain transcriptional silencing, and loss of PcG genes causes widespread derepression of many developmentally important genes. However, because of their broad effects, the degree to which PcG proteins are used at specific fate choice points has not been tested. To understand how fate choices are maintained, we have been analyzing R7 photoreceptor neuron development in the fly eye. R1, R6, and R7 neurons are recruited from a pool of equivalent precursors. In order to adopt the R7 fate, these precursors make three binary choices. They: (1) adopt a neuronal fate, as a consequence of high receptor tyrosine kinase (RTK) activity (they would otherwise become non-neuronal support cells); (2) fail to express Seven-up (Svp), as a consequence of Notch (N) activation (they would otherwise express Svp and become R1/R6 neurons); and (3) fail to express Senseless (Sens), as a parallel consequence of N activation (they would otherwise express Sens and become R8 neurons in the absence of Svp). We were able to remove PcG genes specifically from post-mitotic R1/R6/R7 precursors, allowing us to probe these genes' roles in the three binary fate choices that R1/R6/R7 precursors face when differentiating as R7s.ResultsHere, we show that loss of the PcG genes Sce, Scm, or Pc specifically affects one of the three binary fate choices that R7 precursors must make: mutant R7s derepress Sens and adopt R8 fate characteristics. We find that this fate transformation occurs independently of the PcG genes' canonical role in repressing Hox genes. While N initially establishes Sens repression in R7s, we show that N is not required to keep Sens off, nor do these PcG genes act downstream of N. Instead, the PcG genes act independently of N to maintain Sens repression in R1/R6/R7 precursors that adopt the R7 fate.ConclusionsWe conclude that cells can use PcG genes specifically to maintain a subset of their binary fate choices.

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The Abelson tyrosine kinase regulates Notch endocytosis and signaling to maintain neuronal cell fate inDrosophilaphotoreceptors

Cited by 15 publications

References 38 publications

Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

Past1 Modulates Drosophila Eye Development

Polycomb group genes are required to maintain a binary fate choice in the Drosophila eye

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