Spatial Regulation of nanos Is Required for Its Function in Dendrite Morphogenesis

Abstract

Spatial control of mRNA translation can generate cellular asymmetries and functional specialization of polarized cells like neurons. A requirement for the translational repressor Nanos (Nos) in the Drosophila larval peripheral nervous system (PNS) implicates translational control in dendrite morphogenesis [1]. Nos was first identified by its requirement in the posterior of the early embryo for abdomen formation [2]. Nos synthesis is targeted to the posterior pole of the oocyte and early embryo through translational repression of unlocalized nos mRNA coupled with translational activation of nos mRNA localized at the posterior pole [3, 4]. Abolishment of nos localization prevents abdominal development, whereas translational derepression of unlocalized nos mRNA suppresses head/thorax development, emphasizing the importance of spatial regulation of nos mRNA [3, 5]. Loss and overexpression of Nos affect dendrite branching complexity in class IV dendritic arborization (da) neurons, suggesting that nos also might be regulated in these larval sensory neurons [1]. Here, we show that localization and translational control of nos mRNA are essential for da neuron morphogenesis. RNA-protein interactions that regulate nos translation in the oocyte and early embryo also regulate nos in the PNS. Live imaging of nos mRNA shows that the cis-acting signal responsible for posterior localization in the oocyte/embryo mediates localization to the processes of class IV da neurons but suggests a different transport mechanism. Targeting of nos mRNA to the processes of da neurons may reflect a local requirement for Nos protein in dendritic translational control.

Novel roles for Nanos in neural cell fate determination revealed by studies in a cnidarian

“…Second, it is crucial for germ cell development, where it mediates self-renewal of germ stem cells, their migration to the gonads, and suppresses somatic fate and premature differentiation (Hayashi et al, 2004). Finally, Nanos fulfils some functions in the nervous system of Drosophila (Ye et al, 2004;Brechbiel and Gavis, 2008). Nanos expression patterns in various animals are consistent with these functions.…”

“…Lastly, the function of Nanos in the nervous system is by far the least well studied. Work done in Drosophila has shown that Nanos is required for dendrite morphogenesis (Ye et al, 2004;Brechbiel and Gavis, 2008) through an unclear mechanism. In the mouse, Nanos1 is expressed in the central nervous system, but its function is unidentified (Haraguchi et al, 2003).…”

Lighting up mRNA localization inDrosophilaoogenesis

“…The system was adapted for transgenic use in Drosophila to investigate nos mRNA localization in late oocytes (Forrest and Gavis, 2003), and has been subsequently applied to grk, bcd and osk (Jaramillo et al, 2008;Weil et al, 2006;Zimyanin et al, 2008) (Fig. 1C-F), as well as to several neuronal mRNAs (Ashraf et al, 2006;Brechbiel and Gavis, 2008;Estes et al, 2008). A major strength of this system is the production of fluorescent transcripts, at or near physiological levels, that have been subject to endogenous processing steps.…”

Dendritically Localized Transcripts Are Sorted into Distinct Ribonucleoprotein Particles That Display Fast Directional Motility along Dendrites of Hippocampal Neurons

“…Many groups have routinely assessed RNA localization by in situ hybridization (ISH) in either cultured dissociated neurons or in brain slices. Recently, novel methods have been developed to directly visualize individual dendritic RNAs [e.g., microinjection of fluorescently labeled RNAs in living hippocampal neurons (Shan et al, 2003;Gao et al, 2008) and the MS2 system (Brechbiel and Gavis, 2008;Dictenberg et al, 2008)]. The first two mentioned studies focused on the molecular mechanism of dendritic RNA localization; the latter studied the kinetics of RNA transport in living neurons.…”