The Transcription Factor Cux1 Regulates Dendritic Morphology of Cortical Pyramidal Neurons

Li, Ning; Zhao, Chuntao; Wang, Ying; Yuan, Xiao-bing

doi:10.1371/journal.pone.0010596

Cited by 59 publications

(51 citation statements)

References 47 publications

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“…Although the importance of Cut/Cux1/Cux2 has been well established in neuronal specification and dendrite development (Grueber et al, 2003;Iulianella et al, 2009;Cubelos et al, 2010;Li et al, 2010) it is only recently that studies have begun to unravel the machinery underlying Cut-mediated regulation of dendritic elaboration in da neurons (Sulkowski et al, 2011;Iyer et al, 2012;Nagel et al, 2012). Our results show that gene expression cascades initiated by Cut regulate a specific subcellular function, COPII transport, as one important means of mediating large-scale changes in cellular morphology.…”

Section: Discussionmentioning

confidence: 68%

“…Several studies have focused on the identification and characterization of transcription factors that function to specify and control dendritic growth, branching and cytoskeletal rearrangements (Jan and Jan, 2010;Corty et al, 2009;Ye et al, 2011;Iyer et al, 2012;Nagel et al, 2012). For example, members of the Cut/Cux1/Cux2 family of homeodomain transcription factors have been shown to be multilevel regulators of synaptogenesis and dendritic spine morphology in the brain cortex (Cubelos et al, 2010;Li et al, 2010) in the acquisition of class-specific dendritic arbor complexity among Drosophila da neurons as well as (Grueber et al, 2003). In other cases, the combinatorial action of multiple transcription factors operates to specify dendritic arbor shape in individual subtypes (Jinushi-Nakao et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Cut via CrebA transcriptionally regulates the COPII secretory pathway to direct dendrite development inDrosophila

Iyer

Meduri

et al. 2013

Journal of Cell Science

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SummaryDendrite development is crucial in the formation of functional neural networks. Recent studies have provided insights into the involvement of secretory transport in dendritogenesis, raising the question of how the secretory pathway is controlled to direct dendritic elaboration. Here, we identify a functional link between transcriptional regulatory programs and the COPII secretory machinery in driving dendrite morphogenesis in Drosophila dendritic arborization (da) sensory neurons. MARCM analyses and gain-of-function studies reveal cell-autonomous requirements for the COPII coat protein Sec31 in mediating da neuron dendritic homeostasis. We demonstrate that the homeodomain protein Cut transcriptionally regulates Sec31 in addition to other components of COPII secretory transport, to promote dendrite elaboration, accompanied by increased satellite secretory endoplasmic reticulum (ER) and Golgi outposts primarily localized to dendritic branch points. We further establish a novel functional role for the transcription factor CrebA in regulating dendrite development and show that Cut initiates a gene expression cascade through CrebA that coordinately affects the COPII machinery to mediate dendritic morphology.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Cut via CrebA transcriptionally regulates the COPII secretory pathway to direct dendrite development inDrosophila

Iyer

Meduri

et al. 2013

Journal of Cell Science

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“…Mammalian orthologs of Cut, termed Cut-like 1 and 2 (Cux1 and Cux2), have been characterized and may have conserved functions in dendrite morphogenesis. In mammalian cortical pyramidal neurons, Cux1 but not Cux2 appears to reduce dendrite complexity by suppressing the expression of p27Kip1 (also known as Cdkn1b) and regulating RhoA (Li et al, 2010b). Other studies suggest that Cux1 and Cux2 operate in a cell-intrinsic manner to stimulate the growth and branching of dendrites in upper layer cortical neurons (Cubelos et al, 2010).…”

Section: Transcriptional Control Of Dendrite Morphogenesis In the Mammentioning

confidence: 99%

Cell-intrinsic drivers of dendrite morphogenesis

Puram

Bonni

2013

Development

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The proper formation and morphogenesis of dendrites is fundamental to the establishment of neural circuits in the brain. Following cell cycle exit and migration, neurons undergo organized stages of dendrite morphogenesis, which include dendritic arbor growth and elaboration followed by retraction and pruning. Although these developmental stages were characterized over a century ago, molecular regulators of dendrite morphogenesis have only recently been defined. In particular, studies in Drosophila and mammalian neurons have identified numerous cell-intrinsic drivers of dendrite morphogenesis that include transcriptional regulators, cytoskeletal and motor proteins, secretory and endocytic pathways, cell cycle-regulated ubiquitin ligases, and components of other signaling cascades. Here, we review cell-intrinsic drivers of dendrite patterning and discuss how the characterization of such crucial regulators advances our understanding of normal brain development and pathogenesis of diverse cognitive disorders. KEY WORDS: Cell-intrinsic driver, Dendrite development, Dendrite morphogenesis, Dendrite patterning, Transcription factor, Ubiquitin ligases IntroductionWith their tremendous complexity and diversity, dendrites are one of nature's architectural masterpieces. More than a century ago, Ramón y Cajal proposed an important role for dendrites (referred to at that time as protoplasmic processes) as specialized morphological structures that receive neuronal input (Ramón y Cajal, 1995). Further studies using a variety of neuronal cell types (see Glossary, Box 1) have vastly improved our understanding of dendrite development (Scott and Luo, 2001;Grueber and Jan, 2004). The development of new approaches for studying dendrite morphogenesis (see Box 2) has led to the view that axons and dendrites work in concert to define neuronal connectivity. A key concept that has emerged from such functional studies is that the particular shapes of dendrites are intimately tied to the proper wiring of neuronal circuits and their function (Häusser et al., 2000;Parrish et al., 2007b;Branco et al., 2010;Branco and Häusser, 2011;Gidon and Segev, 2012; Lavzin et al., 2012).Prior to the elaboration of dendrites, neurons undergo axodendritic polarization, whereby the morphologically and functionally distinct axonal and dendritic compartments (see Box 3) are specified. In most neurons, including retinal ganglion neurons, forebrain pyramidal neurons and cerebellar granule neurons, the generation of an axon precedes the development and elaboration of dendrites (Ramón y Cajal, 1995). Although individual neuronal cell Anterodorsal and lateral projection neurons (aPNs and lPNs). These neurons of the Drosophila antennal lobe are crucial for olfactory processing. They receive excitatory input from olfactory receptor neurons in glomeruli and transmit signals to the mushroom body and lateral horn. Cerebellar granule neurons. The most numerous neurons of the brain, these offer an ideal system for biochemical, morphological and physiological studi...

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“…Subsequent work in Drosophila implicated cut in the regulation of dendrite branching pattern (38 -41). A similar function in the brain of mammals has now been established for the orthologs of cut (42)(43)(44)(45). There are two Cut homeobox genes in mammals, Cux1 and Cux2, that fulfill additive and complementary roles in the stimulation of dendrite branching, spine development, and synapse formation in layer II-III neurons of the cerebral cortex (43,45,46).…”

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 75%

CUX2 Protein Functions as an Accessory Factor in the Repair of Oxidative DNA Damage

Pal

Ramdzan

Kaur

et al. 2015

Journal of Biological Chemistry

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Background: CUX2 contains three Cut repeat domains and is expressed in postmitotic neurons. Results: Cut repeats stimulate the OGG1 DNA glycosylase, and lower or higher CUX2 expression, respectively, delays or accelerates repair of oxidative DNA damage. Conclusion: CUX2 functions as an accessory factor in base excision repair. Significance: CUX2 contributes to the maintenance of genome integrity in long lived neurons.

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The Transcription Factor Cux1 Regulates Dendritic Morphology of Cortical Pyramidal Neurons

Cited by 59 publications

References 47 publications

Cut via CrebA transcriptionally regulates the COPII secretory pathway to direct dendrite development inDrosophila

Cut via CrebA transcriptionally regulates the COPII secretory pathway to direct dendrite development inDrosophila

Cell-intrinsic drivers of dendrite morphogenesis

CUX2 Protein Functions as an Accessory Factor in the Repair of Oxidative DNA Damage

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