Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites

Abstract

Dendritic fields are important determinants of neuronal function. However, how neurons establish and then maintain their dendritic fields is not well understood. Here we show that Polycomb group (PcG) genes are required for maintenance of complete and nonoverlapping dendritic coverage of the larval body wall by Drosophila class IV dendrite arborization (da) neurons. In esc, Su(z)12, or Pc mutants, dendritic fields are established normally, but class IV neurons display a gradual loss of dendritic coverage, while axons remain normal in appearance, demonstrating that PcG genes are specifically required for dendrite maintenance. Both multiprotein Polycomb repressor complexes (PRCs) involved in transcriptional silencing are implicated in regulation of dendrite arborization in class IV da neurons, likely through regulation of homeobox (Hox) transcription factors. We further show genetic interactions and association between PcG proteins and the tumor suppressor kinase Warts (Wts), providing evidence for their cooperation in multiple developmental processes including dendrite maintenance.[Keywords: Drosophila; neuron; dendrite; Polycomb; homeobox; tumor suppressor] Supplemental material is available at http://www.genesdev.org. Received November 20, 2006; revised version accepted February 26, 2007. Dendrite arborization patterns are important for neuronal function and proper wiring of neuronal circuitry. Moreover, sensory perception in some cases depends on complete and nonredundant coverage of the receptive field by dendrites of functionally related neurons, a phenomenon known as tiling. For example, many types of neurons tile the mammalian retina, most likely to ensure efficient and unambiguous representation of the visual field. At least 11 distinct physiological classes of rabbit retinal ganglion cells (RGCs) cover their receptive field nonredundantly by avoiding overlap between dendrites of a single neuron as well as between dendrites of the same type of neurons, whereas dendrites of different types of neurons freely cross one another (Wassle et al. 1978(Wassle et al. , 1983Rockhill et al. 2002). Similarly, >20 classes of amacrine cells in the rabbit retina can be distinguished on the basis of dendrite morphology, and many of these classes of amacrine cells appear to tile the retina. Sensory neurons in Manduca, Drosophila, and the leech Hirudu medicinalis also exhibit tiling, suggesting that tiling may be a general mechanism to organize dendritic fields Grueber and Jan 2004).Once neurons tile their receptive field and achieve complete coverage during development, the tiling is maintained even as the territory changes; for example, as the animal grows in size. Whereas like-repels-like homotypic repulsion is one mechanism important for the establishment of receptive fields (Grueber et al. 2003b), how tiling is maintained after the establishment of the dendritic field is not well understood. Underscoring the potential physiological significance of the maintenance of dendritic fields, dendrites of layer III cortical ...

Hippo signaling pathway and organ size control

“…85 The specification of posterior follicle cell fate identify during oogenesis, another process that involves Hpo signaling, does not require the action of Fat. 81 These observations indicate that there can be deviations from the canonical pathway depending on developmental contexts. With respect to situations in which the Hpo pathway goes awry, Yap is upregulated in many cancers but the underlying mechanisms and functional significance remain largely undetermined.…”

“…12 The biological effect of Hpo signaling is likely to be context dependent, and there is evidence that Yap can promote cell death by binding to a p53 family member, p73. 77,78 In Drosophila, Hpo pathway components also play roles in other developmental processes including retina cell patterning, 79 dendrite morphogenesis, 80,81 regulation of oocyte polarity [82][83][84] and salivary gland degeneration. 85 Furthermore, Hpo signaling regulates salivary gland cell death in a PI3K-dependent, but Yki-independent, manner.…”

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

“…In addition, some pathways showed evidence supportive of transheterozygous mutations, that is, heterozygous mutations in 2 genes in a common pathway [181]. This genetic mechanism is commonly encountered in model organisms [182]; however, this mechanism of inheritance has not been exhaustively studied. Homozygosity mapping was also used to identify novel rare, recessive loci in syndromes including autism symptoms.…”

Molecular and cellular mechanisms of dendritic morphogenesis

“…The opposing effects of Cut and Abrupt indicate that they control the expression of distinct subsets of target genes, which remain to be identified. Another example of neuronal type-specific regulation was elucidated in a recent study on the Polycomb group (PcG) genes [31], which bind to specific regions of the genome and initiating the posttranslational modification of histones for gene silencing [32]. Interestingly, PcG gene activities seem to be required to maintain dendritic arbors of class IV only but not other DA neurons.…”

“…These surprising findings indicate that the cell-intrinsic "ruler" plays a predominant role in determining dendritic field size. Similarly, wildtype class IV DA neurons in Drosophila exhibit normal dendritic fields when adjacent PcG mutant neurons fail to maintain their dendrites at the late larval stage [31], suggesting that dendritic repulsion is not required for maintaining mature dendritic field. However, laser ablation during embryogenesis [31,[50][51][52] or in early larval stages [51,52] does result in the invasion of developing dendrites from adjacent neurons.…”