Mcidas and GemC1/Lynkeas specify embryonic radial glial cells

Kyrousi, Christina; Lalioti, Maria‐Eleni; Skavatsou, Eleni; Lygerou, Zoi; Taraviras, Stavros

doi:10.1080/23262133.2016.1172747

Cited by 14 publications

(14 citation statements)

References 34 publications

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“…GemC1, a member of the geminin family, has been shown to promote the generation of MCCs across different cell tissues and animal models (Arbi et al, 2016(Arbi et al, , 2018Kyrousi et al, 2015Kyrousi et al, , 2016Kyrousi et al, , 2017Terré et al, 2016;Zhou et al, 2015). Its role was mainly attributed to its ability to activate transcription of Mcidas, Foxj1 and Myb genes encoding key transcription factors for early events in commitment and differentiation of MCCs.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, specific recognition of the different gene targets in each process could be determined by differential interactions and the formation of multiprotein complexes that can provide cellular specificity. GemC1 and McIdas are key factors regulating the generation of MCCs (Arbi et al, 2018;Kyrousi et al, 2016Kyrousi et al, , 2017Ma et al, 2014;Stubbs et al, 2012;Terré et al, 2016;Zhou et al, 2015). It has been shown that they interact with E2F-family members and activate transcription through promoter-located E2F-binding sites in genes important for multiciliogenesis, including those of transcription factors ΜYB, FOXJ1 and MCIDAS (Arbi et al, 2016;Kyrousi et al, 2015;Ma et al, 2014;Terré et al, 2016).…”

Section: Gemc1 Binds To P73 and Recruits It To E2f5-containing Complexesmentioning

confidence: 99%

“…Recent findings have emphasized the role of the geminin family members McIdas (also known as Idas) (Pefani et al, 2011) and geminin coiled-coil domain-containing protein 1 (GMNC; also known as Lynkeas; hereafter referred to as GemC1) (Balestrini et al, 2010), to multiciliate cell fate acquisition and differentiation (reviewed in Arbi et al, 2018;Kyrousi et al, 2016Kyrousi et al, , 2017. GemC1 had initially been identified as a cell cycle regulator, essential for the initiation of DNA replication during the transition from G1 to S phase (Balestrini et al, 2010) but was later shown to constitute a key molecule in the early steps of multiciliate cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

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GemC1 governs multiciliogenesis through direct interaction with and transcriptional regulation of p73

Lalioti

Arbi

Loukas

et al. 2019

Journal of Cell Science

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A distinct combination of transcription factors elicits the acquisition of a specific fate and the initiation of a differentiation program. Multiciliated cells (MCCs) are a specialized type of epithelial cells that possess dozens of motile cilia on their apical surface. Defects in cilia function have been associated with ciliopathies that affect many organs, including brain and airway epithelium. Here we show that the geminin coiled-coil domain-containing protein 1 GemC1 (also known as Lynkeas) regulates the transcriptional activation of p73, a transcription factor central to multiciliogenesis. Moreover, we show that GemC1 acts in a trimeric complex with transcription factor E2F5 and tumor protein p73 (officially known as TP73), and that this complex is important for the activation of the p73 promoter. We also provide in vivo evidence that GemC1 is necessary for p73 expression in different multiciliated epithelia. We further show that GemC1 regulates multiciliogenesis through the control of chromatin organization, and the epigenetic marks/tags of p73 and Foxj1. Our results highlight novel signaling cues involved in the commitment program of MCCs across species and tissues. This article has an associated First Person interview with the first author of the paper.

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Section: Discussionmentioning

confidence: 99%

Section: Gemc1 Binds To P73 and Recruits It To E2f5-containing Complexesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GemC1 governs multiciliogenesis through direct interaction with and transcriptional regulation of p73

Lalioti

Arbi

Loukas

et al. 2019

Journal of Cell Science

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“…A subset of radial glial cells also gives rise to ependymal cells (Merkle, Tramontin, García‐Verdugo, & Alvarez‐Buylla, ; Spassky et al, ). The commitment to the ependymal lineage occurs in a similar developmental stage, when radial glial cells become post‐mitotic and complete their differentiation within the first two postnatal weeks (Kyrousi et al, ; Kyrousi, Lalioti, Skavatsou, Lygerou, & Taraviras, ; Kyrousi, Lygerou, & Taraviras, ; Spassky et al, ). Nevertheless, whether adult NSCs and ependymal cells are derived from a common subpopulation of radial glial cells remains poorly characterized (Kyrousi et al, ; Wang, Kane, Lee, & Ahn, ).…”

Section: Introductionmentioning

confidence: 99%

“…We and others have formerly shown that GemC1 , a member of the Geminin superfamily, is implicated in cellular differentiation events of multiciliated cells in several tissues (Arbi et al, ; Chong, Zhang, Zhou, & Roy, ; Terré et al, ; Zhou et al, ), and that it is a key regulator for ependymal lineage commitment in the CNS (Kyrousi et al, , , ). The present study demonstrates a novel mutation in the GEMC1 coiled coil domain identified in a human patient with congenital hydrocephalus.…”

Section: Introductionmentioning

confidence: 99%

GemC1 is a critical switch for neural stem cell generation in the postnatal brain

Lalioti

Kaplani

Lokka

et al. 2019

Glia

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The subventricular zone (SVZ) is one of two main niches where neurogenesis persists during adulthood, as it retains neural stem cells (NSCs) with self‐renewal capacity and multi‐lineage potency. Another critical cellular component of the niche is the population of postmitotic multiciliated ependymal cells. Both cell types are derived from radial glial cells that become specified to each lineage during embryogenesis. We show here that GemC1, encoding Geminin coiled‐coil domain‐containing protein 1, is associated with congenital hydrocephalus in humans and mice. Our results show that GemC1 deficiency drives cells toward a NSC phenotype, at the expense of multiciliated ependymal cell generation. The increased number of NSCs is accompanied by increased levels of proliferation and neurogenesis in the postnatal SVZ. Finally, GemC1‐knockout cells display altered chromatin organization at multiple loci, further supporting a NSC identity. Together, these findings suggest that GemC1 regulates the balance between NSC generation and ependymal cell differentiation, with implications for the pathogenesis of human congenital hydrocephalus.

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How a radial glial cell decides to become a multiciliated ependymal cell

Kyrousi

Lygerou

Taraviras

2017

Glia

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The V-SVZ adult neurogenic niche is located in the wall of the lateral ventricles and contains neural stem cells, with self-renewing and differentiating ability and postmitotic multiciliated ependymal cells, an important structural and trophic component of the niche. The niche is established at postnatal stages from a subpopulation of radial glial cells, determined during embryogenesis. Radial glial cells constitute a heterogeneous population, which give rise, in addition to niche cellular components, to neurons and glial cells. The mechanisms that direct their fate commitment towards V-SVZ niche cells are largely unknown. In the present review, we discuss recent findings on the signaling networks governing fate commitment decisions of radial glial cells towards multiciliated ependymal cells. We highlight the role of two novel factors: McIdas and GemC1/Lynkeas and the molecular pathways which they activate in order to promote ependymal cell differentiation. Finally, we discuss a possible crosstalk of known signaling pathways, such as Notch, STAT3, and BMPs, for the specification of ependymal versus adult neural stem cells in the V-SVZ niche. GLIA 2017;65:1032-1042.

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Mcidas and GemC1/Lynkeas specify embryonic radial glial cells

Cited by 14 publications

References 34 publications

GemC1 governs multiciliogenesis through direct interaction with and transcriptional regulation of p73

GemC1 governs multiciliogenesis through direct interaction with and transcriptional regulation of p73

GemC1 is a critical switch for neural stem cell generation in the postnatal brain

How a radial glial cell decides to become a multiciliated ependymal cell

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