FACS Purification and Transcriptome Analysis of Drosophila Neural Stem Cells Reveals a Role for Klumpfuss in Self-Renewal

Berger, Christian; Harzer, Heike; Burkard, Thomas R; Steinmann, Jonas; Horst, Suzanne van der; Laurenson, Anne-Sophie; Novatchkova, Maria; Reichert, Heinrich; Knoblich, Juergen A.

doi:10.1016/j.celrep.2012.07.008

Cited by 129 publications

(173 citation statements)

References 71 publications

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“…Together with the wts loss of function data (Fig. 5 B and B′′), this suggests that Wts may not be expressed in the CB, although hpo and wts transcripts are detectable in NBs (84). Alternatively, Wts could be inactive in the larval CB in late developmental stages, or its Yki-repressing activity may be overridden by that of LKB1, which acts in parallel to restrain Yki.…”

Section: Significancementioning

confidence: 93%

Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system

Gailite

Aerne

Tapon

2015

Proc. Natl. Acad. Sci. U.S.A.

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The Hippo (Hpo) pathway is a highly conserved tumor suppressor network that restricts developmental tissue growth and regulates stem cell proliferation and differentiation. At the heart of the Hpo pathway is the progrowth transcriptional coactivator Yorkie [Yki–Yes-activated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) in mammals]. Yki activity is restricted through phosphorylation by the Hpo/Warts core kinase cascade, but increasing evidence indicates that core kinase-independent modes of regulation also play an important role. Here, we examine Yki regulation in the Drosophila larval central nervous system and uncover a Hpo/Warts-independent function for the tumor suppressor kinase liver kinase B1 (LKB1) and its downstream effector, the energy sensor AMP-activated protein kinase (AMPK), in repressing Yki activity in the central brain/ventral nerve cord. Although the Hpo/Warts core cascade restrains Yki in the optic lobe, it is dispensable for Yki target gene repression in the late larval central brain/ventral nerve cord. Thus, we demonstrate a dramatically different wiring of Hpo signaling in neighboring cell populations of distinct developmental origins in the central nervous system.

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Section: Significancementioning

confidence: 93%

Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system

Gailite

Aerne

Tapon

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Hence, we used the transcriptome data to determine if there is evidence for delayed development in T1 EW, and if there is broad support for a reduced ventral contribution to the T1 EW. First, to address developmental timing, we examined expression of lama, a gene that preserves the pluripotency of disc cells and is not expressed after tissue determination (34). lama was more highly expressed in T2 and T3 wings whereas it was nearly undetectable in T1 EW and the T1 body wall (Fig.…”

Section: Insights About Wing Origins and Functionalization From T1 Ecmentioning

confidence: 99%

Origin and diversification of wings: Insights from a neopteran insect

Medved

Marden

Fescemyer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Winged insects underwent an unparalleled evolutionary radiation, but mechanisms underlying the origin and diversification of wings in basal insects are sparsely known compared with more derived holometabolous insects. In the neopteran species Oncopeltus fasciatus, we manipulated wing specification genes and used RNA-seq to obtain both functional and genomic perspectives. Combined with previous studies, our results suggest the following key steps in wing origin and diversification. First, a set of dorsally derived outgrowths evolved along a number of body segments including the first thoracic segment (T1). Homeotic genes were subsequently co-opted to suppress growth of some dorsal flaps in the thorax and abdomen. In T1 this suppression was accomplished by Sex combs reduced, that when experimentally removed, results in an ectopic T1 flap similar to prothoracic winglets present in fossil hemipteroids and other early insects. Global geneexpression differences in ectopic T1 vs. T2/T3 wings suggest that the transition from flaps to wings required ventrally originating cells, homologous with those in ancestral arthropod gill flaps/epipods, to migrate dorsally and fuse with the dorsal flap tissue thereby bringing new functional gene networks; these presumably enabled the T2/T3 wing's increased size and functionality. Third, "fused" wings became both the wing blade and surrounding regions of the dorsal thorax cuticle, providing tissue for subsequent modifications including wing folding and the fit of folded wings. Finally, Ultrabithorax was co-opted to uncouple the morphology of T2 and T3 wings and to act as a general modifier of hindwings, which in turn governed the subsequent diversification of lineage-specific wing forms.wing origins | Sex combs reduced | Ultrabithorax | RNA-seq | vestigial S ome 350 million years ago, the development of insect wings was a seminal event in the evolution of insect body design (1, 2). The ability to fly was critical to insects becoming the most diverse and abundant animal group, and the origin of such novelty has been a focus of intense scientific inquiry for more than a century (3, 4). More recently, through studies of genetic model systems such as Drosophila, the mechanisms of wing morphogenesis have been elucidated (5-12). Still lacking however is a comprehensive understanding of transitional steps connecting the morphology of structures observed in the fossil record with that of the modern-day insects, including wing origins and subsequent diversification.The initial stages of insect wing evolution are missing from the fossil record and it is therefore necessary to use indirect evidence from fossils that postdate the origin and initial radiation of pterygotes (2). Larvae of many of those taxa featured dorsally positioned outgrowths on each of the thoracic and abdominal segments (2, 13), apparently serial homologs (i.e., similar structures likely arising from a common set of developmental mechanisms). Diverse lineages independently lost those dorsal appendages on the abdomen while un...

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“…Recently, further insight into the molecular mechanisms of brain tumour formation has been obtained in Drosophila by combining genome-wide RNAi screens for genes involved in neuroblast overproliferation with methods for isolation and purification of normal and abnormal neuroblasts (Neumüller et al 2011;Berger et al 2012). These studies show that the type II neuroblasts, which amplify proliferation through INPs, are especially vulnerable to tumorigenic misregulation (figure 4).…”

Section: Aberration: Defects In Neural Stem Cell Proliferation Cause mentioning

confidence: 99%

Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster

Reichert

2014

J Biosci

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Groundbreaking work by Obaid Siddiqi has contributed to the powerful genetic toolkit that is now available for studying the nervous system of Drosophila. Studies carried out in this powerful neurogenetic model system during the last decade now provide insight into the molecular mechanisms that operate in neural stem cells during normal brain development and during abnormal brain tumorigenesis. These studies also provide strong support for the notion that conserved molecular genetic programs act in brain development and disease in insects and mammals including humans.[Reichert H 2014 Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster. J.

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FACS Purification and Transcriptome Analysis of Drosophila Neural Stem Cells Reveals a Role for Klumpfuss in Self-Renewal

Cited by 129 publications

References 71 publications

Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system

Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system

Origin and diversification of wings: Insights from a neopteran insect

Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster

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