The Glial Regenerative Response to Central Nervous System Injury Is Enabled by Pros-Notch and Pros-NFκB Feedback

Kato, Kentaro; Forero, Manuel G.; Fenton, J. C.; Hidalgo, Alicia

doi:10.1371/journal.pbio.1001133

Cited by 65 publications

(175 citation statements)

References 80 publications

(110 reference statements)

Supporting

Mentioning

170

Contrasting

Order By: Relevance

“…Others have shown that Prospero can activate glial gene expression (Choksi et al, 2006;Kato et al, 2011), and our data here suggested that Prospero might play an active role in instructing astrocytic fate. We misexpressed Prospero specifically in Prospero − LG using R56F03-Gal4 (Fig.…”

Section: Prospero Itself Drives Astrocyte Differentiationsupporting

confidence: 76%

“…Astrocyte cell bodies consistently occupied particular regions around the neuropil (Fig. 1I), comparable to their positions seen in third-instar larval VNC (Ito et al, 1995;Kato et al, 2011;Stork et al, 2014). Indeed, among the six astrocytes by hemisegment, three are at dorsal positions, two are more laterally located and one is ventral.…”

Section: Drosophila Astrocytes Infiltrate Specific Neuropil Territoriessupporting

confidence: 65%

“…RNAi knockdown of Prospero itself abolished Ebony expression (Fig. 5J,J′) (Kato et al, 2011) and prevented astrocyte infiltration into the neuropil (Fig. 5K-Lb′).…”

Section: Notch and Prospero Promote Astrogenesis At The Expense Of Enmentioning

confidence: 93%

“…Glutamine synthetase 2 (Thomas and van Meyel, 2007) and the N-β-alanyl-biogenic amine synthetase Ebony (Kato et al, 2011) were shown to be expressed in Prospero + glia. Also, mRNAs for Eaat1, the only Drosophila glutamate transporter (Besson et al, 2000), and Eaat2, a transporter for taurine and aspartate (Besson et al, 2005(Besson et al, , 2011(Besson et al, , 2000, were shown to be expressed in discrete subsets of glia in the embryonic CNS (Freeman et al, 2003; Soustelle et al, 2002;Stacey et al, 2010).…”

Section: Astrocytes and Ensheathing Glia Are Distinguished By Expressmentioning

confidence: 98%

“…In vertebrates, Prospero-related homeobox 1 (Prox1) is expressed in astrocyte-like Müller cells of the retina of adult mammals and fish (Cid et al, 2010) and other glial cells (Lavado and Oliver, 2007), but whether it is involved in glial differentiation remains unknown. Interestingly, Drosophila glia expressing Prospero and Ebony have been shown to regenerate in response to stab injury in the larval VNC (Kato et al, 2011). Knowing now that these cells are astrocytes adds to the intriguing list of functions that Drosophila astrocytes share with their mammalian counterparts.…”

Section: Astrocyte Generation From a Multipotent Glioblast Requires Pmentioning

confidence: 99%

See 4 more Smart Citations

Drosophila astrocytes cover specific territories of CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch

et al. 2016

View full text Add to dashboard Cite

Astrocytes are crucial in the formation, fine-tuning, function and plasticity of neural circuits in the central nervous system. However, important questions remain about the mechanisms instructing astrocyte cell fate. We have studied astrogenesis in the ventral nerve cord of Drosophila larvae, where astrocytes exhibit remarkable morphological and molecular similarities to those in mammals. We reveal the births of larval astrocytes from a multipotent glial lineage, their allocation to reproducible positions, and their deployment of ramified arbors to cover specific neuropil territories to form a stereotyped astroglial map. Finally, we unraveled a molecular pathway for astrocyte differentiation in which the Ets protein Pointed and the Notch signaling pathway are required for astrogenesis; however, only Notch is sufficient to direct non-astrocytic progenitors toward astrocytic fate. We found that Prospero is a key effector of Notch in this process. Our data identify an instructive astrogenic program that acts as a binary switch to distinguish astrocytes from other glial cells.

show abstract

Section: Prospero Itself Drives Astrocyte Differentiationsupporting

confidence: 76%

Section: Drosophila Astrocytes Infiltrate Specific Neuropil Territoriessupporting

confidence: 65%

“…RNAi knockdown of Prospero itself abolished Ebony expression (Fig. 5J,J′) (Kato et al, 2011) and prevented astrocyte infiltration into the neuropil (Fig. 5K-Lb′).…”

Section: Notch and Prospero Promote Astrogenesis At The Expense Of Enmentioning

confidence: 93%

Section: Astrocytes and Ensheathing Glia Are Distinguished By Expressmentioning

confidence: 98%

Section: Astrocyte Generation From a Multipotent Glioblast Requires Pmentioning

confidence: 99%

See 3 more Smart Citations

Drosophila astrocytes cover specific territories of CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch

et al. 2016

View full text Add to dashboard Cite

show abstract

Glial Cells in Neural Development

Trébuchet¹,

Giangrande²

2012

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Glial cells and neurons depend on each other from birth to death. Glial cells accomplish many tasks for the proper development of the nervous system and for the maintenance of neurological functions. This review focuses on recent findings in the simple Drosophila model and underlines the similarities and differences between fly and vertebrate glia. The molecular and cellular mechanisms underlying gliogenesis will be reviewed as well as the role of the master regulatory gene of the glial fate: glial cells deficient / glial cells missing (glide/gcm). All along the review, the features shared between glia and macrophages are highlighted, as glide/gcm is also required in macrophage development and fly glia behave as nervous system‐specific scavenger cells. Finally, the recent data about the developmental pathways and the role of fly glia prompt us to reconsider the origin of glial cells during evolution. Key Concepts: Glial cells are very diversified in terms of morphology, function and gene expression profile. Glial cells are absolutely required for nervous system development and to support neuronal functions. Vertebrate and invertebrate nervous systems share many similarities. Glial cells are the immune cells of the Drosophila nervous system. Glial cells are very dynamic and migrate collectively over long distances. Most glia and neurons arise from common precursors. glide/gcm transcription factor represents the master gene of the glial fate in Drosophila acting as a genetic switch between neuron and glia. glide/gcm is expressed and required in Drosophila glia and macrophages. Glia and macrophages share molecular and cellular pathways. The gcm ortholog genes are not necessary in vertebrate glial development.

show abstract

Gene network underlying the glial regenerative response to central nervous system injury

Kato

Losada‐Pérez

Hidalgo

2017

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

Although the central nervous system does not regenerate, injury induces repair and regenerative responses in glial cells. In mammals, activated microglia clear up apoptotic cells and debris resulting from the injury, astrocytes form a scar that contains the lesion, and NG2-glia elicit a prominent regenerative response. NG2-glia regenerate themselves and differentiate into oligodendrocytes, which remyelinate axons leading to some recovery of locomotion. The regenerative response of glial cells is evolutionarily conserved across the animals and Drosophila genetics revealed an underlying gene network. This involves the genes Notch, kon-tiki, eiger, dorsal, and prospero, homologues of mammalian Notch1, ng2, TNF, NFjB, and prox1, respectively. Feedback loops between these genes enable a surge in proliferation in response to injury and ensuing differentiation. Negative feedback sets a timer for proliferation, and prevents uncontrolled growth that could lead to glioma. Remarkable parallels are found in these genetic relationships between fruit flies and mammals. Drosophila findings provide insights into gene functions that could be manipulated in stem cells and progenitors for therapeutic repair. Developmental Dynamics 247:85-93, 2018. V C 2017 Wiley Periodicals, Inc.

show abstract

The Glial Regenerative Response to Central Nervous System Injury Is Enabled by Pros-Notch and Pros-NFκB Feedback

Abstract: A gene network involving Notch and Pros underlies the glial regenerative response to injury in the Drosophila central nervous system.

Cited by 65 publications

References 80 publications

Drosophila astrocytes cover specific territories of CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch

Drosophila astrocytes cover specific territories of CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch

Glial Cells in Neural Development

Gene network underlying the glial regenerative response to central nervous system injury

Contact Info

Product

Resources

About