A Signaling Network for Patterning of Neuronal Connectivity in the Drosophila Brain

Srahna, Mohammed; Leyssen, Maarten; Choi, Ching Man; Fradkin, Lee G.; Noordermeer, Jasprina N.; Hassan, Bassem A.

doi:10.1371/journal.pbio.0040348

Cited by 64 publications

(67 citation statements)

References 74 publications

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“…Alternatively, JNK activation may act as a reprogramming signal allowing neurons to reactivate their specific developmental pathways. Although we do not exclude a role for JNK in axonal navigation, our previous work (Leyssen et al, 2005;Srahna et al, 2006) shows that JNK can stimulate different cell types to grow longer axons, without influencing their guidance properties. In this context, it may seem surprising that the induction of JNK signaling observed during axonal injury (Leyssen et al, 2005) is not sufficient to induce regeneration.…”

Section: Jnk Signaling Regulates Axonal Regenerationmentioning

confidence: 57%

“…First, JNK is a general stress response pathway (Leppa and Bohmann, 1999). Second, we have shown that JNK signaling is necessary and sufficient for axonal extension in the fly CNS (Srahna et al, 2006) and that it is transiently induced by brain injury in Drosophila (Leyssen et al, 2005). Third, c-Jun is necessary for spontaneous regeneration in the mouse PNS (Raivich et al, 2004).…”

Section: Activated Jnk Signaling Induces Regeneration Back Into the Omentioning

confidence: 99%

“…To test a role for JNK in CNS axonal regeneration, we inactivated JNK signaling solely in the adult LNv neurons by overexpressing a dominant-negative allele of the Drosophila JNK Basket (Bsk DN ) (Boutros et al, 1998;Reed et al, 2001;Srahna et al, 2006) and examined axonal regeneration using the three main criteria described above. Adult-specific inhibition of JNK signaling in injured LNv does not significantly alter the percentage of brains or single axons showing regrowth [43.7%, n ϭ 16, pϭ 0.26 and 10.9% (7 of 64), p ϭ 0.059, respectively] (Figs.…”

Section: Activated Jnk Signaling Induces Regeneration Back Into the Omentioning

confidence: 99%

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Axonal Injury and Regeneration in the Adult Brain of Drosophila

Ayaz¹,

Leyssen²,

Koch³

et al. 2008

Journal of Neuroscience

105

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Drosophila melanogaster is a leading genetic model system in nervous system development and disease research. Using the power of fly genetics in traumatic axonal injury research will significantly speed up the characterization of molecular processes that control axonal regeneration in the CNS. We developed a versatile and physiologically robust preparation for the long-term culture of the whole Drosophila brain. We use this method to develop a novel Drosophila model for CNS axonal injury and regeneration. We first show that, similar to mammalian CNS axons, injured adult wild-type fly CNS axons fail to regenerate, whereas adult-specific enhancement of protein kinase A activity increases the regenerative capacity of lesioned neurons. Combined, these observations suggest conservation of neuronal regeneration mechanisms after injury. We next exploit this model to explore pathways that induce robust regeneration and find that adultspecific activation of c-Jun N-terminal protein kinase signaling is sufficient for de novo CNS axonal regeneration injury, including the growth of new axons past the lesion site and into the normal target area.

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Section: Jnk Signaling Regulates Axonal Regenerationmentioning

confidence: 57%

Section: Activated Jnk Signaling Induces Regeneration Back Into the Omentioning

confidence: 99%

Section: Activated Jnk Signaling Induces Regeneration Back Into the Omentioning

confidence: 99%

See 1 more Smart Citation

Axonal Injury and Regeneration in the Adult Brain of Drosophila

Ayaz¹,

Leyssen²,

Koch³

et al. 2008

Journal of Neuroscience

105

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“…We asked whether DenMark could be used to identify the dendritic compartments of sparse or individual neurons by labeling the dorsal cluster neurons (DCNs) in the adult brain (38) and a pair of eclosion hormone (EH) positive neurons in the third instar larva. DCN axons innervate the lobula and medulla of the optic lobes contralaterally, whereas their dendrites have been proposed to innervate the ipsilateral lobula only (39). Syt:: GFP and DenMark were expressed in the DCN and their patterns examined (Fig.…”

Section: Denmark Reveals Progressive Developmental Specialization Ofmentioning

confidence: 99%

Genetically encoded dendritic marker sheds light on neuronal connectivity inDrosophila

Nicolaï

Ramaekers

Raemaekers

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

266

227

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In recent years, Drosophila melanogaster has emerged as a powerful model for neuronal circuit development, pathology, and function. A major impediment to these studies has been the lack of a genetically encoded, specific, universal, and phenotypically neutral marker of the somatodendritic compartment. We have developed such a marker and show that it is effective and specific in all neuronal populations tested in the peripheral and central nervous system. The marker, which we name DenMark (Dendritic Marker), is a hybrid protein of the mouse protein ICAM5/Telencephalin and the red fluorescent protein mCherry. We show that DenMark is a powerful tool for revealing novel aspects of the neuroanatomy of developing dendrites, identifying previously unknown dendritic arbors, and elucidating neuronal connectivity.T o discover neuronal circuit architecture, genetic tools that specifically mark the pre-and postsynaptic cells and compartments are necessary. Drosophila is a leading genetic model organism in this regard; however, most neuronal circuits remain unmapped. Of particular note is the lack of a universal, phenotypically neutral, and specific marker of the somatodendritic and postsynaptic compartments. Several molecular differences between dendrites and axons, including the presence of different membrane and cytoskeletal proteins in neuronal subregions, have been identified (1, 2). Drosophila neurons exhibit the major kinds of compartmentalization present in mammalian neurons and the fly has emerged as a powerful system to study the establishment and maintenance of neuronal connections (3, 4). Almost all studies of neuronal circuits in the fly have relied on genetic markers such as CD8::GFP that outline the morphology of entire cells rather than particular subcellular compartments (5), as well as presynaptic markers such as Synaptotagmin, Synaptobrevin, and Bruchpilot GFP fusion proteins (6-11). However, more accurate identification and mapping of novel neuronal circuits has been hampered by the lack of a genetically encoded and phenotypically neutral dendritic marker. Over the years, many such markers have been proposed and several were recently examined (12), namely MAP2 (13, 14), Nod::YFP (4, 15-18), Homer::GFP (19), and DSCAM17.1::GFP (20, 21). The analysis of these markers reveals that none of them labels the entire somatodendritic field. Furthermore, it remains unclear whether the markers tested are neutral with respect to dendritic morphology.Intercellular adhesion molecules (ICAMs) mediate neuronal migration, axon elongation, and fasciculation, synaptogenesis, and synaptic plasticity (22). ICAM5, or Telencephalin, is a 130-kDa type I transmembrane glycoprotein comprising a characteristic extracellular domain, a single transmembrane region, and a short cytoplasmic region (23). The expression of ICAM5 is restricted to the mammalian brain telencephalon (24) but there is no homolog in invertebrates and lower vertebrates. The developmental appearance of ICAM5 parallels the time of dendritic elongation, branching, a...

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“…As a member of the JIPs, JIP3 has been suggested to tether specific JNK signaling modules, thereby promoting signal transmission (3)(4)(5)(6). The JNK pathway is involved in axon formation/polarization, extension, synaptic plasticity, and dendrite development (7)(8)(9)(10)(11). Moreover, as a homology of UNC-16 in Caenorhabditis elegans and Sunday Driver in Drosophila, JIP3 is implicated as an adaptor protein in kinesin-dependent vesicular transport to axons (12,13) and has recently been reported to be a mediator in TrkB anterograde axonal transport in hippocampal neurons (14).…”

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confidence: 99%