Biochemical Purification of a Mammalian Slit Protein as a Positive Regulator of Sensory Axon Elongation and Branching

Wang, Kuan Hong; Brose, Katja; Arnott, David; Kidd, Thomas; Goodman, Corey S.; Henzel, William J.; Tessier‐Lavigne, Marc

doi:10.1016/s0092-8674(00)80588-7

Cited by 439 publications

(349 citation statements)

References 44 publications

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“…Dutt1 also was expressed by dorsal root ganglia (DRG), but not Robo1. DRG expression contrasts with a previous study using probes that detected both Robo1/Dutt1 isoforms, which failed to label E13-17 rat spinal cord DRGs while a Robo2 probe did Wang et al, 1999). The differing results may reflect a higher sensitivity of our probes, or a species difference.…”

Section: Dutt1 Has Broad Expression In Neuronal and Non-neuronal Tissuecontrasting

confidence: 91%

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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Section: Dutt1 Has Broad Expression In Neuronal and Non-neuronal Tissuecontrasting

confidence: 91%

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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“…95 Slit proteins also repel migrating muscle precursors in fly embryos 87 and mesodermal cells in zebrafish embryos. 96 However, in rodents Slit2 can stimulate axonal elongation and branch formation of sensory axons from the dorsal root ganglia 97 and attract migrating cells in Drosophila embryo. 98 Roundabout (robo) proteins are the Slit receptors.…”

Section: The Slits and Robosmentioning

confidence: 99%

The brain within the tumor: new roles for axon guidance molecules in cancers

2005

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Slits, semaphorins and netrins are three families of proteins that can attract or repel growing axons and migrating neurons in the developing nervous system of vertebrates and invertebrates. Recent studies have shown that they are widely expressed outside the nervous system and that they may play important roles in cancers. Several of the genes encoding these proteins are localized on chromosomal region associated with frequent loss-of-heterozygosity in tumors and cancer cell lines and there is also significant hypermethylation of their promoter suggesting that they may act as tumor suppressors. In addition, proteins in all these families and their receptors appear to control the vascularization of the tumors. Last, many axon guidance molecules also regulate cell migration and apoptosis in normal and tumorigenic tissues. Overall, this suggests that molecules that could mimick or block the activity of axon guidance molecules may be used as therapeutic agents for the treatment of malignancy.

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“…The expression patterns of mammalian robo1 and 2 have been studied in the developing spinal cord Wang et al, 1999;, eye (Erskine et al, 2000;Niclou et al, 2000;Ringstedt et al, 2000), kidney (Piper et al, 2000), olfactory bulb, and hippocampus (Nguyen Ba-Charvet et al, 1999). Mammalian robo1 expression also has been described in somites, limb buds, and trigeminal ganglia (W. .…”

Section: What Are the Roles Of Zebrafish Robos During Embryogenesis?mentioning

confidence: 99%

Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration

Lee

Ray

Chien

2001

Developmental Dynamics

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We report the cloning and expression patterns of three novel zebrafish Roundabout homologs. The Roundabout (robo) gene encodes a transmembrane receptor that is essential for axon guidance in Drosophila and Robo family members have been implicated in cell migration. Analysis of extracellular domains and conserved cytoplasmic motifs shows that zebrafish Robo1 and Robo2 are orthologs of mammalian Robo1 and Robo2, respectively, while zebrafish Robo3 is likely to be an ortholog of mouse Rig-1. The three zebrafish robos are expressed in distinct but overlapping patterns during embryogenesis. They are highly expressed in the developing nervous system, including the olfactory system, visual system, hindbrain, cranial ganglia, spinal cord, and posterior lateral line primordium. They are also expressed in several nonneuronal tissues, including somites and fin buds. The timing and patterns of expression suggest roles for zebrafish robos in axon guidance and cell migration. Wiley-Liss, Inc.

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Biochemical Purification of a Mammalian Slit Protein as a Positive Regulator of Sensory Axon Elongation and Branching

Cited by 439 publications

References 44 publications

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

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

The brain within the tumor: new roles for axon guidance molecules in cancers

Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration

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