MAP kinase subcellular localization controls both pattern and proliferation in the developing<i>Drosophila</i>wing

Marenda, Daniel R.; Vrailas, Alysia D.; Rodrigues, Aloma B.; Cook, Summer; Powers, Maureen A.; Lorenzen, James A.; Perkins, Lizabeth A.; Moses, Kevin

doi:10.1242/dev.02168

Cited by 41 publications

(54 citation statements)

References 52 publications

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“…In addition to its known role in promoting cell cycle progression, it has been suggested that subcellular localization of ERK regulates distinct cellular responses (Marenda et al, 2006;Chuderland et al, 2008). ERK nuclear shuttling is mediated by a nuclear translocation sequence (NTS) within the kinase insert domain of ERK.…”

Section: Resultsmentioning

confidence: 99%

Nuclear to cytoplasmic shuttling of ERK promotes differentiation of muscle stem/progenitor cells

et al. 2014

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The transition between the proliferation and differentiation of progenitor cells is a key step in organogenesis, and alterations in this process can lead to developmental disorders. The extracellular signal-regulated kinase 1/2 (ERK) signaling pathway is one of the most intensively studied signaling mechanisms that regulates both proliferation and differentiation. How a single molecule (e.g. ERK) can regulate two opposing cellular outcomes is still a mystery. Using both chick and mouse models, we shed light on the mechanism responsible for the switch from proliferation to differentiation of head muscle progenitors and implicate ERK subcellular localization. Manipulation of the fibroblast growth factor (FGF)-ERK signaling pathway in chick embryos in vitro and in vivo demonstrated that blockage of this pathway accelerated myogenic differentiation, whereas its activation diminished it. We next examined whether the spatial subcellular localization of ERK could act as a switch between proliferation (nuclear ERK) and differentiation (cytoplasmic ERK) of muscle progenitors. A myristoylated peptide that blocks importin 7-mediated ERK nuclear translocation induced robust myogenic differentiation of muscle progenitor/stem cells in both head and trunk. In the mouse, analysis of Sprouty mutant embryos revealed that increased ERK signaling suppressed both head and trunk myogenesis. Our findings, corroborated by mathematical modeling, suggest that ERK shuttling between the nucleus and the cytoplasm provides a switch-like transition between proliferation and differentiation of muscle progenitors.

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Section: Resultsmentioning

confidence: 99%

Nuclear to cytoplasmic shuttling of ERK promotes differentiation of muscle stem/progenitor cells

et al. 2014

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“…Another possibility is that enough pMAPK can translocate into the nucleus in the absence of Msk to perform some functions, but that levels are not sufficient for others. Third, some functions of pMAPK may be via cytoplasmic targets, which do not require nuclear translocation, as is known in the developing wing (Marenda et al, 2006).…”

Section: Msk Is Normally Required For Cell Proliferation and Survivalmentioning

confidence: 99%

“…However, we have been unable to identify Drosophila Pea15 or Sef homologs by BLAST analysis. Another possible mediator of MAPK cytoplasmic hold in Drosophila may be the Drosophila homolog of vertebrate importin 7, Moleskin (Msk), which has been found to bind pMAPK and is involved in its nuclear transport, with reported roles in embryonic and wing development (Lorenzen et al, 2001;Baker et al, 2002;Marenda et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

smoothenedandthickveinsregulate Moleskin/Importin 7-mediated MAP kinase signaling in the developingDrosophilaeye

et al. 2006

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The Drosophila Mitogen Activated Protein Kinase (MAPK) Rolled is a key regulator of developmental signaling, relaying information from the cytoplasm into the nucleus. Cytoplasmic MEK phosphorylates MAPK (pMAPK), which then dimerizes and translocates to the nucleus where it regulates transcription factors. In cell culture, MAPK nuclear translocation directly follows phosphorylation, but in developing tissues pMAPK can be held in the cytoplasm for extended periods (hours). Here, we show that Moleskin antigen (Drosophila Importin 7/Msk), a MAPK transport factor, is sequestered apically at a time when lateral inhibition is required for patterning in the developing eye. We suggest that this apical restriction of Msk limits MAPK nuclear translocation and blocks Ras pathway nuclear signaling. Ectopic expression of Msk overcomes this block and disrupts patterning. Additionally, the MAPK cytoplasmic hold is genetically dependent on the presence of Decapentaplegic (Dpp) and Hedgehog receptors.

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“…Consistent with this observation, loss-of-function mutations of the Ras/ERK pathway components result in loss of veins, whereas gain-offunction alleles and/or overexpression of these components induce ectopic vein development (Brunner et al, 1994;Kim et al, 2006;Prober and Edgar, 2000;Sturtevant and Bier, 1995). Additionally, phosphorylated cytoplasmic ERK promotes vein differentiation in the developing wing vein and margin cells during the larval and early pupal stage (Marenda et al, 2006). Thus, Ras/ERK is critical for the control of vein differentiation and proliferation in Drosophila.…”

Section: Introductionmentioning

confidence: 99%

The BTB/POZ-ZF Transcription Factor dPLZF Is Involved in Ras/ERK Signaling During Drosophila Wing Development

Maeng

Son

Chung

et al. 2012

Molecules and Cells

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In Drosophila, broad complex, tramtrack, bric à brac (BTB)/ poxvirus and zinc finger (POZ) transcription factors are essential regulators of development. We searched the Drosophila genome for BTB/POZ-ZF domains and discovered an unknown Drosophila gene, dPLZF, which encodes an orthologue of human PLZF. We then characterized the biological function of the dPLZF via genetic interaction analysis. Ectopic expression of dPLZF in the wing induced extra vein formation during wing development in Drosophila. Genetic interactions between dPLZF and Ras or extracellular signal-regulated kinase (ERK) significantly enhanced the formation of vein cells. On the other hand, loss-of-function mutations in dPLZF resulted in a dramatic suppression of the extra and ectopic vein formation induced by elevated Ras/ERK signaling. Moreover, dPLZF activity upregulated the expression of rhomboid (rho) and spitz, which perform crucial functions in vein cell formation in the developing wing. These results indicate that dPLZF is a transcription factor controlled by the Ras/ERK signaling pathway, which is a prominent regulator of vein cell formation during wing development in Drosophila.

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MAP kinase subcellular localization controls both pattern and proliferation in the developingDrosophilawing

Cited by 41 publications

References 52 publications

Nuclear to cytoplasmic shuttling of ERK promotes differentiation of muscle stem/progenitor cells

Nuclear to cytoplasmic shuttling of ERK promotes differentiation of muscle stem/progenitor cells

smoothenedandthickveinsregulate Moleskin/Importin 7-mediated MAP kinase signaling in the developingDrosophilaeye

The BTB/POZ-ZF Transcription Factor dPLZF Is Involved in Ras/ERK Signaling During Drosophila Wing Development

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