Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract

Thompson, Hannah; Barker, David; Camand, Olivier; Erskine, Lynda

doi:10.1016/j.ydbio.2006.06.017

Cited by 45 publications

(53 citation statements)

References 45 publications

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“…As of yet, ephrins have no reported role in guidance within the diencephalon or at the target border. In comparison, a subset of RGC axons project aberrantly into the epithalamus, in the pineal gland, and across the dorsal midline in mice lacking both slit1 and slit2 (Thompson et al, 2006). This phenotype is similar to that we observed with ADAM10 inhibition at the mid-diencephalic turn.…”

Section: Discussionsupporting

confidence: 84%

Targeting of Retinal Axons Requires the Metalloproteinase ADAM10

Chen

Hehr²,

Atkinson‐Leadbeater³

et al. 2007

J. Neurosci.

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The role of extrinsic cues in guiding developing axons is well established; however, the means by which the activity of these extrinsic cues is regulated is poorly understood. A disintegrin and metalloproteinase (ADAM) enzymes are Zn-dependent proteinases that can cleave guidance cues or their receptors in vitro. Here, we identify the first example of a metalloproteinase that functions in vertebrate axon guidance in vivo. Specifically, ADAM10 is required for formation of the optic projection by Xenopus retinal ganglion cell (RGC) axons. Xadam10 mRNA is expressed in the dorsal neuroepithelium through which RGC axons extend. Pharmacological or molecular inhibition of ADAM10 within the brain each resulted in a failure of RGC axons to recognize their target. In contrast, molecular inhibition of ADAM10 within the RGC axons themselves had no effect. These data argue strongly that in the dorsal brain ADAM10 acts cell non-autonomously to regulate the guidance of RGC axons.

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Section: Discussionsupporting

confidence: 84%

Targeting of Retinal Axons Requires the Metalloproteinase ADAM10

Chen

Hehr²,

Atkinson‐Leadbeater³

et al. 2007

J. Neurosci.

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“…For example, mice with Robo mutations have defects in midline crossing of spinal cord commissural axons (Long et al, 2004). Other axon populations dependent on Slit/Robo signaling include major forebrain tracts and commissures (Andrews et al, 2006;Bagri et al, 2002), retinal axons (Plump et al, 2002;Thompson et al, 2006), and motor axons (Hammond et al, 2005), as well as others.…”

Section: Resultsmentioning

confidence: 99%

The Slit receptor Robo1 is predominantly expressed via the Dutt1 alternative promoter in pioneer neurons in the embryonic mouse brain and spinal cord

Nural

Farmer

Mastick

2007

Gene Expression Patterns

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Robo1 is a member of the Roundabout (Robo) family of receptors for the Slit axon guidance cues. In mice (and humans), the Robo1 locus has alternative promoters producing two transcript isoforms, Robo1 and Dutt1. These isoforms have unique 5′ termini, predicted to encode distinct N-terminal amino acids, but share the rest of their 3′ exons. To determine the spatial expression of the Robo1 and Dutt1 isoforms, we generated isoform-specific RNA probes, and carried out in situ hybridization on E10.5 mouse embryos, the stage in early neuron differentiation when many major axon pathways are established. The two isoforms had distinct expression patterns that partially overlapped. Dutt1 was the predominant isoform, with widespread expression in regions of post-mitotic neurons and neuroepithelial cells. The Robo1 isoform had a distinct expression pattern restricted to subsets of neurons, many of which were Dutt1-negative. Dutt1 was the main isoform expressed in spinal cord commissural neurons. For both probes, the main hybridization signal was limited to two spots in the nuclei of individual cells. This study shows distinct expression patterns for the Dutt1 and Robo1 alternative promoters in the embryonic nervous system. Keywords axon guidance; neuron; Robo; Slit; longitudinal axon; commissural axon; dorsal root ganglion Results and DiscussionGrowth cones navigate by selectively responding to molecular cues in their environment. Different types of axons differ in their responses to cues, depending on their expression of specific combinations of guidance receptors. In contrast to the great diversity in neuron types and their axon projection patterns, a surprisingly small number of axon guidance receptors have been identified to date. However, single receptor genes could potentially give rise to multiple receptor isoforms through mechanisms such as alternative promoters and differential mRNA splicing.The Slit repellents and their Robo receptors are a major guidance system conserved from invertebrates to vertebrates (Dickson and Gilestro, 2006). The Roundabout (Robo) family of Corresponding author: Grant Mastick, Department of Biology, University of Nevada, Reno NV 89557, Phone: 775-784-6168, FAX: 775-784-1650, gmastick@unr.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. transmembrane receptors was first identified in Drosophila in a mutant screen for genes that control midline crossing by pioneer axons (Seeger et al., 1993). Slit/Robo signaling has a primary function in keeping axons out of the Slit+ midline, both in commissural axons to prevent re-crossing, as well as ...

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“…Slit homolog 1 (Drosophila), higher in the iP line, has been implicated in processes related to neuroplasticity (Table 9), specifically in axon guidance (Chang et al, 2006;Long et al, 2004;Thompson et al, 2006). One of the 21 differentially expressed genes in the HIPP, ribosomal protein S2, was located within established alcohol QTLs Carr et al, 1998Carr et al, ,2003Foroud et al, 2002Foroud et al, ,2003Radcliffe et al, 2004;Terenina-Rigaldie et al, 2003) (Table 5).…”

Section: Within-region Analysismentioning

confidence: 99%

Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

Kimpel

Strother

McClintick

et al. 2007

Alcohol

107

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The objective of this study was to determine if there are innate differences in gene expression in selected CNS regions between inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and hippocampus (HIPP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray Analysis with a false discovery rate threshold of 0.1, there were 16 genes with differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU, and 21 in the HIPP. When examining the main effect of strain across regions, 296 genes were differentially expressed. Although the relatively small number of genes found significant within individual regions precluded a powerful analysis for over-represented Gene Ontology categories, the much larger list resulting from the main effect of strain analysis produced 17 over-represented categories (P <.05), including axon guidance, gliogenesis, negative regulation of programmed cell death, regulation of programmed cell death, regulation of synapse structure function, and transmission of nerve impulse. Co-citation analysis and graphing of significant genes revealed a network involved in the neuropeptide Y (NPY) transmitter system. Correlation of all significant genes with those located within previously established rat alcohol QTLs revealed that of the total of 313 significant genes, 71 are located within such QTLs. The many regional and overall gene expression differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats.

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Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract

Cited by 45 publications

References 45 publications

Targeting of Retinal Axons Requires the Metalloproteinase ADAM10

Targeting of Retinal Axons Requires the Metalloproteinase ADAM10

The Slit receptor Robo1 is predominantly expressed via the Dutt1 alternative promoter in pioneer neurons in the embryonic mouse brain and spinal cord

Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

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