Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system

Flici, Hakima; Cattenoz, Pierre B.; Komonyi, Orbán; Laneve, Pietro; Erkoşar, Berra; Karataş, Ömer Faruk; Reichert, Heinrich; Berzsenyi, Sára; Giangrande, Angela

doi:10.1038/ncomms5484

Cited by 18 publications

(32 citation statements)

References 60 publications

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“…[53][54][55][56] After an initial phase of gliogenesis in which repo expression depends on Gcm, Repo maintains its own expression through autoregulation and becomes independent of Gcm. 56,57 This fits with the recently emerged concept that transiently expressed master genes are relayed by their target genes that code for permanently expressed transcription factors. In line with this idea, repo mutant glia lose the expression of late glial markers (reviewed by Cattenoz and Giangrande 58 ).…”

Section: Interaction Between Gcm and Major Signaling Pathwaysmentioning

confidence: 73%

Revisiting the role of the Gcm transcription factor, from master regulator to Swiss army knife

Cattenoz

Giangrande

2016

Fly

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Master genes are known to induce the differentiation of a multipotent cell into a specific cell type. These molecules are often transcription factors that switch on the regulatory cascade that triggers cell specification. Gcm was first described as the master gene of the glial fate in Drosophila as it induces the differentiation of neuroblasts into glia in the developing nervous system. Later on, Gcm was also shown to regulate the differentiation of blood, tendon and peritracheal cells as well as that of neuronal subsets. Thus, the glial master gene is used in at least 4 additional systems to promote differentiation. To understand the numerous roles of Gcm, we recently reported a genome-wide screen of Gcm direct targets in the Drosophila embryo. This screen provided new insight into the role and mode of action of this powerful transcription factor, notably on the interactions between Gcm and major differentiation pathways such as the Hedgehog, Notch and JAK/STAT. Here, we discuss the mode of action of Gcm in the different systems, we present new tissues that require Gcm and we revise the concept of 'master gene'.

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Section: Interaction Between Gcm and Major Signaling Pathwaysmentioning

confidence: 73%

Revisiting the role of the Gcm transcription factor, from master regulator to Swiss army knife

Cattenoz

Giangrande

2016

Fly

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“…This confirms that reducing the dose of Gcm enhances the fra 3 - mediated phenotype (Figure 3—figure supplement 2b). Furthermore, we crossed the fra 3 mutation with a gcm driver that does not affect the gcm locus, a transgenic line carrying 6Kb of the gcm promoter fused to the Gal4 gene, which is inserted on the third chromosome (Flici et al ., 2014 ). In these wings, we did not observe the enhanced migratory phenotype present in the fra 3 , gcm-Gal4 wings (Figure 3—figure supplement 2c).…”

Section: Resultsmentioning

confidence: 99%

“…Our in vivo and cell transfection data using a Repo expression vector are in line with this hypothesis and suggest that Repo may play a regulatory role in the maintenance of fra at late migratory stages (Figure 9a). It is known that Repo expression first depends on Gcm but subsequently becomes independent of it through autoregulation (Flici et al, 2014), indicating a transition from early to late events in gliogenesis (see model in Figure 9b). We propose that the initial Fra expression in wing glia strictly depends on Gcm and triggers the initiation of migration (see the graph in Figure 3—figure supplement 1e).…”

Section: Discussionmentioning

confidence: 99%

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

Gupta

Kumar

Cattenoz

et al. 2016

eLife

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Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination.DOI: http://dx.doi.org/10.7554/eLife.15983.001

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Section: Competence For Chemical Reprogramming Correlates With a Sexumentioning

confidence: 99%

“…For example, murine pancreatic a-cells that are in the process of reprogramming into pancreatic b-cells pass through a state producing both glucagon (an a-cell product) and insulin (a b-cell product) (Thorel et al 2010). Similarly, Drosophila neural progenitors that are reprogramming into the glial lineage pass through a state producing protein markers of both neural stem cells and glial cells (Flici et al 2011).Our discovery of an intermediate molecular signature in mutants competent for gamete sex reprogramming differs from these previous findings. We have discovered an intermediate state that occurs in the absence of reprogramming but signifies competence to change sexual fate in response to ERK/MAPK pathway inhibition, a phenomenon distinct from but perhaps related to the dynamic transitional states that occur during the reprogramming process itself.…”

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confidence: 99%

Competence for Chemical Reprogramming of Sexual Fate Correlates with an Intersexual Molecular Signature inCaenorhabditis elegans

2014

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In multicellular organisms, genetic programs guide cells to adopt cell fates as tissues are formed during development, maintained in adults, and repaired after injury. Here we explore how a small molecule in the environment can switch a genetic program from one fate to another. Wild-type Caenorhabditis elegans XX adult hermaphrodites make oocytes continuously, but certain mutant XX adults make sperm instead in an otherwise hermaphrodite soma. Thus, puf-8; lip-1 XX adults make only sperm, but they can be switched from sperm to oocyte production by treatment with a small-molecule MEK inhibitor. To ask whether this chemical reprogramming is common, we tested six XX sperm-only mutants, but found only one other capable of cell fate switching, fbf-1; lip-1. Therefore, reprogramming competence relies on genotype, with only certain mutants capable of responding to the MEK inhibitor with a cell fate change. To gain insight into the molecular basis of competence for chemical reprogramming, we compared polyadenylated transcriptomes of competent and noncompetent XX sperm-only mutants in the absence of the MEK inhibitor and hence in the absence of cell fate reprogramming. Despite their cellular production of sperm, competent mutants were enriched for oogenic messenger RNAs relative to mutants lacking competence for chemical reprogramming. In addition, competent mutants expressed the oocyte-specific protein RME-2, whereas those lacking competence did not. Therefore, mutants competent for reprogramming possess an intersexual molecular profile at both RNA and protein levels. We suggest that this intersexual molecular signature is diagnostic of an intermediate network state that poises the germline tissue for changing its cellular fate in response to environmental cues. C ELLS in multicellular organisms acquire specific fates, either during development as tissues are generated or during adulthood as tissues are renewed or repaired. A classical view holds that during development, a cell follows a specific genetic program to determine its differentiated fate, but more recent studies reveal that cells can be induced to switch from one genetic program to another. Such "reprogramming" of a cell fate program can occur in vivo in cancer (Friedl and Alexander 2011;Byun and Gardner 2013), wound healing (Wong et al. 2013), and regeneration (Xin et al. 2013;Ziv et al. 2013). Moreover, reprogramming can be stimulated by introduction of transcription factors (Takahashi and Yamanaka 2006) or small molecules (Morgan et al. 2010;Zhu et al. 2010;Li et al. 2014). Here we explore the effect of genotype on the capacity for a particular case of chemically induced cell fate reprogramming within an organism.The Caenorhabditis elegans germline provides a tractable model for analyses of cell fate reprogramming. The adult germline is an elongate tissue with 2000 cells, including germline stem cells (GSCs) (Figure 1A, yellow). GSCs continuously generate daughter cells that enter the meiotic cell cycle ( Figure 1A, green) and then differentiate as...

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Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system

Cited by 18 publications

References 60 publications

Revisiting the role of the Gcm transcription factor, from master regulator to Swiss army knife

Revisiting the role of the Gcm transcription factor, from master regulator to Swiss army knife

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

Competence for Chemical Reprogramming of Sexual Fate Correlates with an Intersexual Molecular Signature inCaenorhabditis elegans

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