inscuteable and numb mediate asymmetric muscle progenitor cell divisions during Drosophila myogenesis

Carmena, Ana; Murugasu-Oei, Bernadette; Menon, Devi; Jiménez, Fernando; Chia, William

doi:10.1101/gad.12.3.304

Cited by 136 publications

(100 citation statements)

References 44 publications

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“…Numb is known to be a negative regulator of Notch signaling (Rhyu et al 1994;Spana and Doe 1996;Carmena et al 1998). Our findings indicate that Notch is necessary and sufficient for promoting larval NB proliferation and suppressing neuronal differentiation.…”

Section: Discussionmentioning

confidence: 61%

“…In contrast to the well-studied role of Numb as a cell fate determinant during asymmetric divisions of embryonic GMCs, SOPs, or muscle progenitors (Rhyu et al 1994;Spana and Doe 1996;Carmena et al 1998), a role for Numb during NB asymmetric divisions has not been described. We show here that Numb also acts as a tumor suppressor in Drosophila larval brains, and that Numb is a key downstream target of AurA and aPKC in the regulation of NB self-renewal.…”

Section: Discussionmentioning

confidence: 95%

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Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

Wang¹,

Somers²,

Bashirullah³

et al. 2006

Genes Dev.

246

294

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The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides terminally to produce two differentiating neuronal/glial daughters. Here we show that Aurora-A (AurA) acts as a tumor suppressor by suppressing NB self-renewal and promoting neuronal differentiation. In aurA loss-of-function mutants, supernumerary NBs are produced at the expense of neurons. AurA suppresses tumor formation by asymmetrically localizing atypical protein kinase C (aPKC), an NB proliferation factor. Numb, which also acts as a tumor suppressor in larval brains, is a major downstream target of AurA and aPKC. Notch activity is up-regulated in aurA and numb larval brains, and Notch signaling is necessary and sufficient to promote NB self-renewal and suppress differentiation in larval brains. Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway that involved a series of negative genetic interactions. We have identified a novel mechanism for controlling the balance between self-renewal and neuronal differentiation during the asymmetric division of Drosophila larval NBs.[Keywords: Neuroblast; stem cells; asymmetric division; tumor suppressor; self-renewal] Supplemental material is available at http://www.genesdev.org.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 95%

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

Wang¹,

Somers²,

Bashirullah³

et al. 2006

Genes Dev.

246

294

View full text Add to dashboard Cite

show abstract

“…Many of the genes implicated in the asymmetric NB4 / GMC-1 / RP2/sib cell division pathway are known to function in the asymmetric division of other lineages (Ruiz Gomez and Bate 1997;Carmena et al 1998;Paululat et al 1999;Tio et al 2001). To test whether orb2 also has a more general role in asymmetric cell division, we examined cell division patterns in the mesoderm.…”

Section: Orb2 May Have a General Role In Asymmetric Cell Divisionmentioning

confidence: 99%

The Drosophila CPEB Protein Orb2 Has a Novel Expression Pattern and Is Important for Asymmetric Cell Division and Nervous System Function

Hafer

Bhat

et al. 2011

Genetics

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Cytoplasmic polyadenylation element binding (CPEB) proteins bind mRNAs to regulate their localization and translation. While the first CPEBs discovered were germline specific, subsequent studies indicate that CPEBs also function in many somatic tissues including the nervous system. Drosophila has two CPEB family members. One of these, orb, plays a key role in the establishment of polarity axes in the developing egg and early embryo, but has no known somatic functions or expression outside of the germline. Here we characterize the other Drosophila CPEB, orb2. Unlike orb, orb2 mRNA and protein are found throughout development in many different somatic tissues. While orb2 mRNA and protein of maternal origin are distributed uniformly in early embryos, this pattern changes as development proceeds and by midembryogenesis the highest levels are found in the CNS and PNS. In the embryonic CNS, Orb2 appears to be concentrated in cell bodies and mostly absent from the longitudinal and commissural axon tracts. In contrast, in the adult brain, the protein is seen in axonal and dendritic terminals. Lethal effects are observed for both RNAi knockdowns and orb2 mutant alleles while surviving adults display locomotion and behavioral defects. We also show that orb2 funtions in asymmetric division of stem cells and precursor cells during the development of the embryonic nervous system and mesoderm. C YTOPLASMIC polyadenylation element binding (CPEB) family proteins bind to target sequences in the 39-UTR of mRNAs and control their localization and translation. CPEB proteins function in many different biologocial contexts including oogenesis in Xenopus and Drosophila (Lantz et al. 1992(Lantz et al. , 1994Christerson and McKearin 1994;Hake and Richter 1994), synaptic plasticity in the rat hippocampus (Wu et al. 1998), and long-term memory in Aplysia . In Xenopus oocytes, CPEB regulates oocyte maturation. Prior to progesterone stimulation, it functions to repress target mRNAs in conjunction with proteins such as Maskin. After hormone stimulation, CPEB is phosphorylated, and the phosphorylated isoform recruits factors that stimulate poly(A) addition and translational activation of mRNAs that mediate the maturation process. In Drosophila, the CPEB protein Orb is required for oocyte determination and the establishment of the anterior-posterior and dorsal-ventral axes of the developing egg chamber. It functions by promoting the on-site translation of mRNAs that are localized in the developing oocyte, and like the Xenopus oocyte CPEB, its activity is regulated by phosphorylation.Most animals have two or more CPEB genes. Completed genome sequences reveal that humans, mice, and Caenorhabditis elegans have four CPEB genes, but only two CPEBs in Drosophila. The homology between the CPEB proteins is limited to the C-terminal half of the protein, which has two RNA-recognition motif (RRM) domains and a zinc finger domain, while the N-terminal half is highly divergent. Phylogenetic trees indicate that the CPEB genes fall into two differen...

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“…Muscle founders arise from progenitor cells, which are singled out by a process of lateral inhibition mediated by the Delta (Dl)/Notch (N) signalling pathway (Brennan et al, 1999;Carmena et al, 2002;Park et al, 1998). The diversity of founders, corresponding to the diversity of muscle fibres, is generated by the asymmetric division of progenitor cells and the expression of founder-specific combinations of transcription factors (Carmena et al, 1998b;Park et al, 1998; Ruiz Gomez and Bate, 1997). Although all the information required for the specific shape, position and innervation of a given muscle is thought to reside within its founder, the formation of a fully functional syncytial muscle fibre involves fusion between the founder cells and a group of fusioncompetent myoblasts (FCMs).…”

Section: Introductionmentioning

confidence: 99%

Coordinated development of muscles and tendons of theDrosophilaleg

Daczewska²,

et al. 2004

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Since Miller's morphological description, the Drosophila leg musculature and its formation has not been revisited. Here, using a set of GFP markers and confocal microscopy, we analyse Drosophila leg muscle development, and describe all the muscles and tendons present in the adult leg. Importantly, we provide for the first time evidence for tendons located internally within leg segments. By visualising muscle and tendon precursors,we demonstrate that leg muscle development is closely associated with the formation of internal tendons. In the third instars discs, in the vicinity of tendon progenitors, some Twist-positive myoblasts start to express the muscle founder cell marker dumbfounded (duf). Slightly later, in the early pupa, epithelial tendon precursors invaginate inside the developing leg segments, giving rise to the internal string-like tendons. The tendon-associated duf-lacZ-expressing muscle founders are distributed along the invaginating tendon precursors and then fuse with surrounding myoblasts to form syncytial myotubes. At mid-pupation, these myotubes grow towards their epithelial insertion sites, apodemes, and form links between internally located tendons and the leg epithelium. This leads to a stereotyped pattern of multifibre muscles that ensures movement of the adult leg.

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inscuteable and numb mediate asymmetric muscle progenitor cell divisions during Drosophila myogenesis

Cited by 136 publications

References 44 publications

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

The Drosophila CPEB Protein Orb2 Has a Novel Expression Pattern and Is Important for Asymmetric Cell Division and Nervous System Function

Coordinated development of muscles and tendons of theDrosophilaleg

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