Isolation and differential expression of two isoforms of the ROBO2/Robo2 axon guidance receptor gene in humans and mice

Yue, Y.; Grossmann, Bärbel; Galetzka, Danuta; Zechner, Ulrich; Haaf, Thomas

doi:10.1016/j.ygeno.2006.05.011

Cited by 19 publications

(21 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…39 Case II.17, described previously, 12 carries a duplication of 3p12.3 containing part of ROBO2, encoding a receptor for SLIT2 and probably SLIT1, thought to function in axon guidance and cell migration. 40 Case II.21, born SGA, length À3.7 SDS and head circumference À3.1 SDS presented with clinodactily, a protruded [30][31][32][33] Associated with fibrillin-1 function. 31,33 Aldh1a3 and Lrrk1 higher expressed in murine GP; Chsy1 highly expressed in HZ and downregulated with age.…”

Section: Discussionmentioning

confidence: 99%

Copy number variants in patients with short stature

et al. 2013

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Copy number variants in patients with short stature

et al. 2013

View full text Add to dashboard Cite

“…For example, alternative splicing of Robo2 and 3 transcripts results in isoforms with distinct affinity for Slit binding and/or differences in intracellular signaling (Camurri et al, 2004;Yue et al, 2006). Tissue-specific alternative mRNA splicing appears to contribute to the spatial complexity of Robo2 and 3 expression (Challa et al, 2005;Dalkic et al, 2006).…”

Section: Nih Public Accessmentioning

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

View full text Add to dashboard Cite

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 ...

show abstract

“…Alternative splicing in the 5Ј coding sequence can generate two distinct receptor isoforms, A and B, which differ at their N-terminal end. Type A isoforms are longer (16-40 residues) than type B isoforms (Camurri et al, 2005; Kidd et al, 1998;Sundaresan et al, 1998;Yue et al, 2006). In the case of Robo3, alternative splicing by the retention or excision of one intron in the 3Ј coding sequence generates two isoforms that differ in their C-terminal domain, with Robo3.1 being longer than Robo3.2 (Chen et al, 2008a).…”

mentioning

confidence: 99%

Moving away from the midline: new developments for Slit and Robo

2010

View full text Add to dashboard Cite

SummaryIn most tissues, the precise control of cell migration and cellcell interaction is of paramount importance to the development of a functional structure. Several families of secreted molecules have been implicated in regulating these aspects of development, including the Slits and their Robo receptors. These proteins have well described roles in axon guidance but by influencing cell polarity and adhesion, they participate in many developmental processes in diverse cell types. We review recent progress in understanding both the molecular mechanisms that modulate Slit/Robo expression and their functions in neural and non-neural tissue. Key words: Axon guidance, Cell migration, Cell-cell interaction IntroductionIn most organisms, the central nervous system (CNS) develops along a bilateral axis of symmetry located at the midline (Placzek and Briscoe, 2005). During development, the ventral midline or floor plate acts as an organiser through the secretion of diffusible proteins (Placzek and Briscoe, 2005;Gore et al., 2008), which control the growth of axons and dendrites and the migration of neurons across the midline. In the forebrain, glial or neuronal cells delineate the midline (see Glossary, Box 1) and also control axon guidance. For more than two decades, many developmental neurobiologists have tried to understand the mechanisms that control midline crossing in the CNS and to answer some key questions. Firstly, how are commissural axons (see Glossary, Box 1) attracted to the midline and how do their growth cones (see Glossary, Box1) receive and integrate the multiple and contrasting signals released by midline cells? Secondly, what are the molecular and signalling changes that enable commissural axons to leave the midline and often to switch to a longitudinal growth mode? All midline-derived axon guidance factors are expressed at other locations in many developing and mature tissues, where they control a wide range of biological processes.Roundabout receptors (Robo) and their Slit ligands form one of the most crucial ligand-receptor pairings among the axon guidance molecules. Robos were identified in Drosophila in a mutant screen for genes that control the midline crossing of commissural axons (Kidd et al., 1998;Seeger et al., 1993). Similarly, Slit was discovered in Drosophila as a protein secreted by midline glia (Rothberg et al., 1988;Rothberg et al., 1990). Homologues of both proteins have since been discovered in many species (for a review, see . However, the Slit/Robo couple not only functions in axon guidance but also in a variety of developmental Development 137, 1939Development 137, -1952Development 137, (2010 Commissural axons Axons with cell bodies (somata) located on one side of the central nervous system (CNS) that project axons across the midline to contact target cells on the opposite side. Growth cone A specialised bulbous enlargement at the end of growing axons that is characterised by dynamic filamentous extensions, known as filopodia. They sense the environment and respond to adhesi...

show abstract

Isolation and differential expression of two isoforms of the ROBO2/Robo2 axon guidance receptor gene in humans and mice

Cited by 19 publications

References 20 publications

Copy number variants in patients with short stature

Copy number variants in patients with short stature

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

Moving away from the midline: new developments for Slit and Robo

Contact Info

Product

Resources

About