MAB-10/NAB acts with LIN-29/EGR to regulate terminal differentiation and the transition from larva to adult in <i>C. elegans</i>

Harris, David T.; Horvitz, H. Robert

doi:10.1242/dev.065417

Cited by 40 publications

(66 citation statements)

References 62 publications

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“…Finally, this was also observed for RNAi of mab-10 (Fig. 6B), a transcription co-factor that acts in concert with LIN-29 to promote differentiation of the hypodermis (Harris and Horvitz, 2011). Thus, we conclude that let-7 regulates cdk-1 indirectly, in a manner that requires the LIN-29 transcription factor.…”

Section: Let-7 Regulates Cdk-1 Expression In a Lin-29-dependent Mannersupporting

confidence: 77%

A genetic interactome of the let-7 microRNA in C. elegans

Rausch

Ecsedi

Bartake

et al. 2015

Developmental Biology

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The heterochronic pathway controls temporal patterning during Caenorhabditis elegans larval development. The highly conserved let-7 microRNA (miRNA) plays a key role in this pathway, directing the larval-to-adult (L/A) transition. Hence, knowledge of the genetic interactome of let-7 has the potential to provide insight into both control of temporal cell fates and mechanisms of regulation and function of miRNAs. Here, we report the results of a genome-wide, RNAi-based screen for suppressors of let-7 mutant vulval bursting. The 201 genetic interaction partners of let-7 thus identified include genes that promote target silencing activity of let-7, seam cell differentiation, or both. We illustrate the suitability of our approach by uncovering the mitotic cyclin-dependent kinase CDK-1 as a downstream effector of let-7 that affects both seam cell proliferation and differentiation, and by identifying a core set of candidate modulators of let-7 activity, which includes all subunits of the condensin II complex. We propose that the genes identified in our screen thus constitute a valuable resource for studies of the heterochronic pathway and miRNAs.

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Section: Let-7 Regulates Cdk-1 Expression In a Lin-29-dependent Mannersupporting

confidence: 77%

A genetic interactome of the let-7 microRNA in C. elegans

Rausch

Ecsedi

Bartake

et al. 2015

Developmental Biology

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“…Smed-egfr-1 regulates eye-pigment cell differentiation; Smed-egfr-3 seems to be necessary for blastema growth and cell differentiation (Fraguas et al, 2011); and Smed-egfr-5 is required for flame cell maintenance and regeneration, and for guiding branch extension in protonephridia (Rink et al, 2011). These observations are consistent with the demonstrated role of the EGFR signaling pathway in cell differentiation in other organisms (Jones et al, 2009;Lejard et al, 2011;Harris and Horvitz, 2011); for example, EGFR is required for the differentiation of mammary epithelial cells (Mukhopadhyay et al, 2013) and human neural progenitors (Lemcke and Kuznetsov, 2013). Here, we identify egr-4 as a putative target of Smed-egfr-3 (Fig.…”

Section: Egr-4 Rnai Disrupts Head Regeneration Without Impairing the supporting

confidence: 74%

egr-4, a target of EGFR signaling, is required for the formation of the brain primordia and head regeneration in planarians

et al. 2014

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During the regeneration of freshwater planarians, polarity and patterning programs play essential roles in determining whether a head or a tail regenerates at anterior or posterior-facing wounds. This decision is made very soon after amputation. The pivotal role of the Wnt/ β-catenin and Hh signaling pathways in re-establishing anteriorposterior (AP) polarity has been well documented. However, the mechanisms that control the growth and differentiation of the blastema in accordance with its AP identity are less well understood. Previous studies have described a role of Smed-egfr-3, a planarian epidermal growth factor receptor, in blastema growth and differentiation. Here, we identify Smed-egr-4, a zinc-finger transcription factor belonging to the early growth response gene family, as a putative downstream target of Smed-egfr-3. Smed-egr-4 is mainly expressed in the central nervous system and its silencing inhibits anterior regeneration without affecting the regeneration of posterior regions. Single and combinatorial RNA interference to target different elements of the Wnt/β-catenin pathway, together with expression analysis of brain-and anterior-specific markers, revealed that Smed-egr-4: (1) is expressed in two phasesan early Smed-egfr-3-independent phase and a late Smed-egfr-3-dependent phase; (2) is necessary for the differentiation of the brain primordia in the early stages of regeneration; and (3) that it appears to antagonize the activity of the Wnt/β-catenin pathway to allow head regeneration. These results suggest that a conserved EGFR/egr pathway plays an important role in cell differentiation during planarian regeneration and indicate an association between early brain differentiation and the proper progression of head regeneration.

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“…The transcriptional co-factor mab-10/NAB cooperates with lin-29/ZnF to specify the adult seam fate. Loss-of-function mutations of mab-10 do not affect seam cell fusion and adult alae formation, but subsets of seam cells undergo an extra nuclear division after they fuse into the seam syncytium (Harris and Horvitz, 2011). blmp-1 depletion enhanced the penetrance of the extra nuclear division phenotype of mab-10(e1248) (Figure S1C) and worms rarely formed adult alae (Figures 3A and S1B) suggesting that blmp-1 acts downstream or in parallel to mab-10 .…”

Section: Resultsmentioning

confidence: 99%

DRE-1/FBXO11-Dependent Degradation of BLMP-1/BLIMP-1 Governs C. elegans Developmental Timing and Maturation

et al. 2014

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Summary Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. C. elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here we identify the conserved Zn-finger transcription factor BLMP-1 as a substrate of the SCFDRE-1/FBXO11 complex. blmp-1 loss-of-function suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1. blmp-1 also opposed dre-1 for other life history traits including entry into the dauer diapause and longevity. BLMP-1 protein was strikingly elevated upon dre-1 depletion and dysregulated in a stage- and tissue-specific manner. The role of DRE-1 in regulating BLMP-1 stability is evolutionary conserved, as we observed direct protein interaction and degradation function for worm and human counterparts. Taken together, post-translational regulation of BLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C. elegans developmental timing and other life history traits, suggesting this two-protein-module mediates metazoan maturation processes.

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MAB-10/NAB acts with LIN-29/EGR to regulate terminal differentiation and the transition from larva to adult in C. elegans

Cited by 40 publications

References 62 publications

A genetic interactome of the let-7 microRNA in C. elegans

A genetic interactome of the let-7 microRNA in C. elegans

egr-4, a target of EGFR signaling, is required for the formation of the brain primordia and head regeneration in planarians

DRE-1/FBXO11-Dependent Degradation of BLMP-1/BLIMP-1 Governs C. elegans Developmental Timing and Maturation

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