Two divergent <i>slit1</i> genes in zebrafish

Hutson, Lara D.; Jurynec, Michael J.; Yeo, Sang-Yeob; Okamoto, Hitoshi; Chien, Chi-­Bin

doi:10.1002/dvdy.10386

Cited by 50 publications

(45 citation statements)

References 53 publications

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“…Further, slit2 has been proposed as an attractant for robo1 expressing endothelial cells (27) and a repellant for robo4 expressing endothelial cells (12). In zebrafish, of the three slit genes, som expression for slit1a is seen from 10 som stage until 24 hpf in tail som (31), and for slit2 at 16 hpf (16). slit3 is not expressed in som but is observed in motor neurons in the ventral spinal chord of 26 hpf embryos (16).…”

Section: Discussionmentioning

confidence: 99%

roundabout4 is essential for angiogenesis in vivo

Bedell

Yeo

Park

et al. 2005

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

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Stereotypical patterns of vascular and neuronal networks suggest that specific genetic programs tightly control path determination and, consequently, angiogenesis and axon-guidance mechanisms. Our study focuses on one member of the roundabout family of receptors, which traditionally mediate repulsion from the midline. Here, we characterize a fourth member of this family, roundabout4 (robo4), which is the predominant roundabout (robo) that is expressed in embryonic zebrafish vasculature. Gene knockdown and overexpression approaches show that robo4 is essential for coordinated symmetric and directed sprouting of intersomitic vessels and provide mechanistic insights into this process. Also, human robo4 gene functionally compensates for loss of robo4 gene function, suggesting evolutionary conservation. This article reports an endothelial-specific function for a robo gene in vertebrates in vivo.axon guidance ͉ endothelial cell ͉ zebrafish V ascular and neural networks established by angiogenesis and neurogenesis are essential for the regulation of physiological processes. Whether the processes of blood-vessel and peripheralnerve formation are intimately associated at a mechanistic level is a subject of active investigation (1). Recently, description of cellsurface molecules that are shared by neuronal and endothelial cells has suggested that this association may be more prevalent than previously thought. Neuropilin (2), ephrin (3), and plexin (4) are a few examples of molecules that are implicated in both processes. Recently, roundabout (robo), a class of neural guidance receptors that bind slit ligands have joined this group (5). slit-robo signaling mediates axonal repulsion (6) and inhibition of leukocyte migration (7). In vertebrate systems, three robo receptor family members were identified, all with prominent neural expression (8, 9). More recently, a fourth member of the robo gene family, roundabout4 (robo4) was identified (10). Compared with the canonical robo structure, robo4 is smaller in that it possesses only two of the five Ig and two of the three fibronectin domains present in the extracellular component of robo1, robo2, and robo3 (11). robo4 has been described as endothelial-specific, and it binds to slit and inhibits the migration of heterologous cells that express robo4 and primary endothelial cells (12). Although studies of robo4 in endothelial cells suggest that robo signaling is important for regulating endothelial cell migration, there are no reports that document the role of robo signaling in vascular development in vivo. Here, we cloned a zebrafish (Danio rerio) ortholog of human robo4 (hrobo4) and studied its expression and role in vascular development by gene knockdown and overexpression approaches. In contrast to the endothelial-specific expression of murine robo4, zebrafish robo4 is expressed in both endothelial and neural tissues with vascular expression seen in angioblasts, the dorsal aorta (DA), the posterior cardinal vein, and intersomitic vessels (ISV). Morpholino (MO) knockdown of robo...

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Section: Discussionmentioning

confidence: 99%

roundabout4 is essential for angiogenesis in vivo

Bedell

Yeo

Park

et al. 2005

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

Self Cite

199

189

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“…Slit-1 and Slit-2 inhibit RGC axons (Erskine et al, 2000;Niclou et al, 2000;Ringstedt et al, 2000;Plump et al, 2002), and application of SDF-1 in vitro reduces the repulsive action of Slit-2 (Chalasani et al, 2003a). Slit-1a and Slit-1b are both expressed in the zebrafish retina and Slit-3 by the lens, but Slit-2 is not expressed in the retina (Yeo et al, 2001;Hutson and Chien, 2002;Hutson et al, 2003). Thus, silencing of repulsive actions of Slit-1 and/or Slit-3 by SDF-1/ CXCR4 could participate in guiding RGC axons within the zebrafish retina.…”

Section: Discussionmentioning

confidence: 99%

Chemokine Signaling Guides Axons within the Retina in Zebrafish

Li¹,

Shirabe²,

Thisse³

et al. 2005

J. Neurosci.

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Chemokines are a large family of secreted proteins that play an important role in the migration of leukocytes during hematopoiesis and inflammation. Chemokines and their receptors are also widely distributed in the CNS. Although recent investigations are beginning to elucidate chemokine function within the CNS, relatively little is known about the CNS function of this important class of molecules. To better appreciate the CNS function of chemokines, the role of signaling by stromal cell-derived factor-1 (SDF-1) through its receptor, chemokine (CXC motif) receptor 4 (CXCR4), was analyzed in zebrafish embryos. The SDF-1/CXCR4 expression pattern suggested that SDF-1/CXCR4 signaling was important for guiding retinal ganglion cell axons within the retina to the optic stalk to exit the retina. Antisense knockdown of the ligand and/or receptor and a genetic CXCR4 mutation both induced retinal axons to follow aberrant pathways within the retina. Furthermore, retinal axons deviated from their normal pathway and extended to cells ectopically expressing SDF-1 within the retina. These data suggest that chemokine signaling is both necessary and sufficient for directing retinal growth cones within the retina.

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“…We investigated whether inhibition of Slit function similarly affected the SOT formation as did the inhibition of Robo2 function. There are four Slit homologs in zebrafish, and they are differentially expressed in the CNS during zebrafish embryonic development (Yeo et al, 2001;Hutson et al, 2003). We examined the expression of these four Slit homologs in the forebrain regions with whole-mount in situ hybridizations.…”

Section: Inhibition Of Slit or Netrin Function Affects The Sot Or Ac mentioning

confidence: 99%

Robo2–Slit and Dcc–Netrin1 Coordinate Neuron Axonal Pathfinding within the Embryonic Axon Tracts

et al. 2012

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In the embryonic vertebrate brain, early born neurons establish highly stereotyped embryonic axonal tracts along which the neuronal interconnections form. To understand the mechanism underlying neuron axonal pathfinding within the embryonic scaffold of axon tracts, we studied zebrafish anterior dorsal telencephalic (ADt) neuron development. While previous studies suggest the ADt neuronal axons extend along a commissural tract [anterior commissure (AC)] and a descending ipsilateral tract [supraoptic tract (SOT)], it is unclear whether individual ADt neuronal axons choose specific projection paths at the intersection between the AC and the SOT. We labeled individual ADt neurons using a forebrain-specific promoter to drive expression of fluorescent proteins. We found the ADt axonal projection patterns were heterogeneous and correlated with their soma positions. Our results suggest that cell intrinsic differences along the dorsal ventral axis of the telencephalon regulate the axonal projection choices. Next, we determined that the guidance receptors roundabout2 (Robo2) and deleted in colorectal cancer (Dcc) were differentially expressed in the ADt neurons. We showed that knocking down Robo2 function by injecting antisense morpholino oligonucleotides abolished the ipsilateral SOT originating from the ADt neurons. Knocking down Dcc function did not prevent formation of the AC and the SOT. In contrast, the AC was specifically reduced when Netrin1 function was knocked down. Further mechanistic studies suggested that Robo2 responded to the repellent Slit signals and suppressed the attractive Netrin signals. These findings demonstrate how Robo2-Slit and Dcc-Netrin coordinate the axonal projection choices of the developing neurons in the vertebrate forebrain.

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Two divergent slit1 genes in zebrafish

Cited by 50 publications

References 53 publications

roundabout4 is essential for angiogenesis in vivo

roundabout4 is essential for angiogenesis in vivo

Chemokine Signaling Guides Axons within the Retina in Zebrafish

Robo2–Slit and Dcc–Netrin1 Coordinate Neuron Axonal Pathfinding within the Embryonic Axon Tracts

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