Alternatively spliced Robo2 isoforms in zebrafish and rat

Abstract

Robo2, a member of the robo gene family, functions as a repulsive axon guidance receptor as well as a regulator of cell migration and tissue morphogenesis in different taxa. In this study, a novel isoform of the zebrafish robo2 (robo2_tv2), which included an otherwise alternatively spliced exon (CAE), has been characterized. Robo2_tv2 is expressed differentially in most non-neuronal tissues of adult zebrafish whereas robo2_tv1 expression to a great extent is restricted to the brain and eye. In zebrafish, robo2_tv2 exhibits a very-low-level basal expression starting from 1 day post fertilization until the mid-larval stages, at which time its expression increases dramatically and could be detected throughout adulthood. Our findings demonstrate that the amino acid sequence coded by CAE of the robo2 gene is highly conserved between zebrafish and mammals, and also contains conserved motifs shared with robo1 and robo4 but not with robo3. Furthermore, we provide an account of differential transcription of the CAE homolog in various tissues of the adult rat. These results suggest that the alternatively spliced robo2 isoforms may exhibit tissue specificity.

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

“…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).…”

“…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).Robo1 presents a different case, with alternative transcription start sites providing the potential to be independently regulated. A human Robo homolog was independently cloned from breast and small cell lung cancer cell lines as a potential tumor suppressor gene and designated as Dutt1 (Deleted in U-twenty twenty) (Sundaresan et al, 1998).…”

Coordinate Regulation of Stem Cell Competition by Slit-Robo and JAK-STAT Signaling in the Drosophila Testis

“…Our work suggests that adherens junctions may act downstream of Slit-Robo signaling in HSCs. In addition, since Slit-Robo signaling has roles in gonad development in flies and in the mammalian ovary [65], and high throughput expression studies suggest that this signaling pathway is active in the mammalian testis, [66]–[68] it may function there as well. Data we present in the Drosophila testis represent the first mechanistic example of Slit-Robo signaling functioning in an intact adult stem cell niche.…”

Assembly of Lamina-Specific Neuronal Connections by Slit Bound to Type IV Collagen

“…Such a positive, axon growth-promoting function of Slit has previously been reported for various types of sensory neurons in mouse (Wang et al, 1999) and zebrafish (Yeo et al, 2004). While there are no detectable differences in robo2 mRNA expression across the population of RGCs (Lee et al, 2001), the zebrafish robo2 transcript has been shown to be alternatively spliced, giving rise to several isoforms, some of which are present only in certain tissues or developmental stages (Dalkic et al, 2006). In mouse spinal cord, two functionally antagonistic isoforms of Robo3 are present in the commissural neurons (Chen et al, 2008).…”