| 2004 |
SLIT2/ROBO2 signaling in the nephrogenic mesenchyme restricts GDNF expression domain and thereby limits ureteric bud outgrowth to a single site; loss of either SLIT2 or ROBO2 causes anterior expansion of Gdnf expression and supernumerary ureteric buds. |
Mouse knockout (Slit2-/- and Robo2-/- mutants), in situ hybridization for Gdnf expression, histological analysis of kidney development |
Developmental cell |
High |
15130495
|
| 2000 |
Drosophila Robo2 and Robo1 have distinct roles in midline axon guidance; robo,robo2 double mutant phenocopies slit mutant (growth cones enter and fail to leave midline), demonstrating Robo2 is a second Slit receptor that together with Robo1 controls repulsive guidance at the midline. |
Drosophila genetics, double mutant analysis (robo;robo2 and slit), axon immunostaining |
Neuron |
High |
11163264
|
| 2007 |
ROBO2 loss-of-function (translocation disrupting ROBO2) produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro, implicating the SLIT-ROBO2 pathway in vesicoureteral reflux and CAKUT pathogenesis. |
Translocation mapping, dominant-negative in vitro signaling assay, heterozygous mouse models, missense variant segregation analysis |
American journal of human genetics |
High |
17357069
|
| 2015 |
Slit2 acting through Robo1 and Robo2 promotes endothelial cell migration, Rac1 activation, and lamellipodia formation, driving retinal neovascularization; both receptors are required for Slit2- and VEGF-induced Rac1 activation. |
Conditional knockout mice (various Slit/Robo combinations), retinal angiogenesis assay, Rac1 activation assay, lamellipodia imaging, endothelial cell migration assay |
Nature medicine |
High |
25894826
|
| 2002 |
Robo2 (astray) in zebrafish shapes retinal ganglion cell axon pathfinding by preventing and correcting pathfinding errors; robo2 mutant growth cones are larger and more complex, make midline and pre/post-midline errors that are rarely corrected, consistent with Slit2 and Slit3 acting as repulsive ligands via Robo2. |
Fixed-tissue and time-lapse imaging of zebrafish astray/robo2 mutant retinal axons, Slit expression analysis |
Neuron |
High |
11804569
|
| 2012 |
Robo2 is expressed on the basal surface of podocytes and forms a complex with nephrin through the adaptor protein Nck; Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization and acts as a negative regulator of podocyte foot process architecture. |
Co-immunoprecipitation, co-localization studies, in vitro actin polymerization assay, Robo2 knockout mouse analysis, genetic interaction (Robo2 KO crossed to nephrin null) |
Cell reports |
High |
22840396
|
| 2016 |
SLIT2/ROBO2 signaling activates a pathway through SRGAP1 and nonmuscle myosin IIA (NMIIA) in podocytes; MRLC (myosin II regulatory light chain) interacts directly with SRGAP1 and forms a ROBO2/SRGAP1/NMIIA complex in the presence of SLIT2; SLIT2 stimulation inhibits NMIIA activity, decreases focal adhesion formation, and reduces podocyte attachment to collagen. |
Co-immunoprecipitation, direct protein interaction assay, immunostaining, focal adhesion assay, cell adhesion assay, podocyte-specific Robo2 KO mouse, in vivo hypertension model |
JCI insight |
High |
27882344
|
| 2015 |
Robo2 acts in trans (non-cell-autonomously) to inhibit Slit-Robo1 repulsion in pre-crossing commissural axons in Drosophila; Robo2's extracellular domains required for binding to Robo1 are also required for its ability to promote midline crossing, suggesting a receptor-receptor interaction mechanism. |
Drosophila genetics, gain-of-function and rescue assays, cell non-autonomous expression, extracellular domain deletion analysis |
eLife |
High |
26186094
|
| 2008 |
Robo2 receptor on ingressing placode cells interacts with its cognate ligand Slit1 expressed on early migrating cranial neural crest cells to mediate neural crest-placode interactions required for trigeminal ganglion assembly. |
Cell ablation experiments in chick, Robo2 function blocking antibodies, RNAi knockdown of Robo2 and Slit1, in situ hybridization for expression patterns |
Nature neuroscience |
High |
18278043
|
| 2009 |
Slit1-Robo2 signaling modulates N-cadherin protein levels on the placodal cell surface (post-translationally, without changing total N-cadherin mRNA or protein) to regulate placodal cell adhesion during gangliogenesis; blocking Robo2 decreases surface N-cadherin, while increasing Slit-Robo signaling increases it. |
In vivo RNAi, dominant-negative Robo2 expression, N-cadherin manipulation, co-expression rescue experiments, in vivo chick trigeminal ganglion model |
Development (Cambridge, England) |
High |
19934013
|
| 2010 |
Robo1 and Robo2 collaborate to prevent post-crossing commissural axons from reentering gray matter; Robo2 specifically is required for axons to project away from the floor plate into the lateral funiculus, while Robo1 prevents axonal stalling after crossing; epistatic analysis shows the double mutant is less severe than loss of all Slits, suggesting additional Slit receptor(s) exist. |
Mouse combination mutants (Robo1-/-, Robo2-/-, Robo3-/-, Slit1-3 triple mutant), commissural axon trajectory analysis |
The Journal of neuroscience |
High |
20631173
|
| 2007 |
Robo-2 is required in a subset of olfactory sensory neurons (OSNs) for dorsoventral segregation of axons in the olfactory bulb; Slit-1 and Slit-3 expressed in the ventral OB act as repulsive ligands via Robo-2 to prevent dorsal OSN axons from projecting to the ventral OB. |
Robo-2 and Slit-1 knockout mice, olfactory axon tracing, expression analysis |
The Journal of neuroscience |
High |
17715346
|
| 2009 |
Robo2 is the major Slit receptor required for intraretinal axon guidance in mice; Robo1 knockout shows no intraretinal guidance defects, while Robo2 knockout phenocopies Slit1/Slit2 double mutant intraretinal pathfinding errors. |
Robo1 and Robo2 knockout mice, intraretinal axon tracing and pathfinding error quantification |
Developmental biology |
High |
19782674
|
| 2007 |
Slit1a inhibits retinal ganglion cell arborization and synaptogenesis via Robo2 in a cell-autonomous manner; increased arborization in astray/robo2 mutant is phenocopied by dominant-negative Robo2 in single RGCs and rescued by full-length Robo2; Slit1a acts both through Robo2-dependent and Robo2-independent mechanisms. |
Zebrafish astray/robo2 mutant, single-cell arbor imaging, dominant-negative and rescue constructs, morpholino knockdown, synaptic site labeling (YFP-Rab3) |
Neuron |
High |
17640525
|
| 2015 |
ROBO2 restricts the nephrogenic field by limiting epithelial/mesenchymal interactions between the Wolffian duct/ureteric epithelium and mesenchyme; loss of Robo2 fails to separate the mesenchyme from Wolffian duct epithelium, exposing mesenchyme to abnormally high proliferative stimuli, expanding the nephrogenic cord cell number and the metanephric mesenchyme field. |
High-resolution 3D imaging of Robo2-null mouse embryos, ex vivo kidney explant experiments, cell proliferation analysis |
Developmental biology |
High |
26116176
|
| 2014 |
SLIT/ROBO2 signaling in mammary basal cells restricts mammary stem cell (MaSC) renewal by negatively regulating WNT signaling; absence of SLIT/ROBO2 leads to increased nuclear β-catenin and repressed expression of p16(INK4a), delaying MaSC senescence. |
Robo2 conditional knockout mice, mammary stem cell functional assay, β-catenin localization, p16(INK4a) expression analysis |
Stem cell reports |
Medium |
25241737
|
| 2019 |
In Drosophila tendons, Robo2 plays a non-signaling role by promoting Slit cleavage to produce the cleaved Slit N-terminal guidance signal; tendon-specific Robo2 expression (not muscle-specific) rescues muscle patterning defects, and membrane immobilization of Slit-N bypasses the requirement for tendon Robo2. |
Drosophila genetics, tissue-specific RNAi and rescue, membrane-tethered Slit constructs, muscle patterning analysis |
Development (Cambridge, England) |
High |
26400093
|
| 2011 |
Pioneer myoblasts express Robo2 downstream of MyoD and Myf5; sclerotome-derived Slit1 acts through Robo2 to direct pioneer myoblast migration and fiber formation via RhoA; loss of Robo2 or sclerotome-derived Slit1 perturbs directional migration and fiber formation. |
Avian somite inversion experiments, Robo2/Slit1 loss-of-function in chick embryos, RhoA pathway analysis, fiber formation and migration assays |
Development (Cambridge, England) |
High |
21653616
|
| 2019 |
Robo2 contains a cryptic binding site for NELL1 and NELL2 in its first fibronectin type III (FNIII) domain; this site is normally occluded in intact Robo2 and becomes accessible upon acidic conditions or proteolytic digestion; specific amino acids in the FNIII domain critical for NELL1 binding to Robo2 (but not Robo1) were identified by mutagenesis. |
Binding assays (NELL1/2 vs Robo family members), deletion mutant analysis, single amino acid mutagenesis, acidic pH binding experiments |
The Journal of biological chemistry |
Medium |
30700556
|
| 2022 |
Conformational change of the Robo2 ectodomain (hairpin-like structure loosening) at acidic pH unmasks the NELL1/2-binding site; the interaction between Ig-like and FNIII domains maintains the occluded conformation at neutral pH; alternative splicing isoforms affect this conformational equilibrium and NELL1/2-binding affinity. |
FRET-based conformational indicator, size exclusion chromatography, binding assays with isoforms, acidic pH experiments |
Journal of molecular biology |
Medium |
35940226
|
| 2019 |
Robo2 regulates synaptic oxytocin content by controlling local actin dynamics via Cdc42; robo2 mutant zebrafish show decreased synaptic OXT levels, reduced Lifeact-EGFP mobility in OXT synapses, and slower vesicle accumulation; dominant-negative Cdc42 (a downstream effector of Robo2) modulates OXT content, placing Slit3-Robo2-Cdc42 in a pathway controlling actin dynamics at OXT synapses. |
Zebrafish robo2 mutant, live imaging of OXT vesicles and actin probe, FRAP, dominant-negative Cdc42 expression, genetic epistasis |
eLife |
High |
31180321
|
| 2021 |
Robo2 acts postsynaptically in hippocampal CA1 pyramidal neurons to promote formation of excitatory (but not inhibitory) synapses specifically in proximal dendritic compartments; this synaptogenic activity involves a trans-synaptic interaction with presynaptic Neurexins and also binding to its canonical ligand Slit. |
In vivo conditional KO, in vitro synaptogenesis assays, co-immunoprecipitation (Robo2-Neurexin interaction), 2-photon Ca2+ imaging of place cells in behaving mice |
Cell reports |
High |
34686348
|
| 2019 |
Robo2 binds Baiap2 (IRSp53) through its IRSp53/MIM homology domain in renal epithelial cells; this interaction allows Robo2 to phosphorylate MDM2 at Ser166 via Baiap2, maintaining p53 homeostasis; disruption of Robo2-Baiap2 complex causes MDM2 dephosphorylation, elevated active p53, p53-mediated cellular senescence via p21, and decreased polarity/ciliary proteins, leading to cystic kidney disease. |
Co-immunoprecipitation, phosphorylation assays, Robo2 KO and double KO (Robo2/p53) mouse models, ciliogenesis and polarity analysis |
JCI insight |
High |
31534052
|
| 2018 |
Epithelial Robo2 loss in the pancreas leads to activation of Robo1+ myofibroblasts and induction of TGF-β and Wnt pathways in a non-cell-autonomous manner; TGF-β inhibitor galunisertib suppresses the myofibroblast activation, collagen crosslinking, and immune infiltration caused by Robo2 loss. |
Pdx1Cre;Robo2F/F conditional KO mice, pancreatitis and PDAC mouse models, cell culture, TGF-β inhibitor treatment, collagen analysis |
Nature communications |
High |
30504844
|
| 2012 |
Robo2 acts as the predominant receptor directing dorsal longitudinal axon tract formation in mouse spinal cord and also has a distinct function in repelling neuron cell bodies from the floor plate; Robo1 is the predominant receptor for ventral longitudinal tracts. |
Conditional reduction of Robo levels in mouse embryos, genetic sensitization strategy, longitudinal axon tract imaging |
Developmental biology |
Medium |
21820427
|
| 2013 |
Robo2 and Dcc coordinate zebrafish ADt neuron axonal projection choices; Robo2 responds to repellent Slit signals and suppresses attractive Netrin signals; knockdown of Robo2 abolishes the ipsilateral SOT projection from ADt neurons. |
Zebrafish morpholino knockdown of Robo2 and Dcc/Netrin1, single-cell labeling of ADt neurons, projection pattern analysis |
The Journal of neuroscience |
Medium |
22956848
|
| 2019 |
Mammalian ROBO1 and ROBO2 are subject to temporal regulation via alternative splicing at a conserved microexon; NOVA splicing factors regulate developmental expression of ROBO1 and ROBO2 variants with distinct guidance activities; early isoforms activate axonal repulsion to prevent premature crossing, later isoforms allow crossing, and postcrossing isoforms are disinhibited. |
Alternative splicing analysis, NOVA splicing factor mutant mice, commissural axon guidance assays, isoform-specific functional assays |
eLife |
High |
31392959
|
| 2014 |
Robo3.1A promotes degradation of Robo2 protein by recruiting it into a late endosome- and lysosome-dependent pathway; cotransfection of Robo3.1A significantly reduces Robo2 protein levels in HEK293 cells and cerebellar granule cells; Robo2 and Robo3 colocalize in intracellular vesicles positive for late endosome/lysosome markers. |
Cotransfection experiments, cell surface binding assay, co-immunoprecipitation, siRNA knockdown, immunocytochemical colocalization with organelle markers |
Journal of neuroscience research |
Medium |
24936616
|
| 2021 |
Robo2 function in regenerating peripheral nerve axons is required and sufficient for target-selective regeneration at nerve branch-points; Robo2 acts in response to locally positioned glia to prevent and correct axonal errors during regeneration. |
Zebrafish motor nerve regeneration model, cell-type-specific expression and knockdown of robo2, live imaging, glia ablation |
The Journal of neuroscience |
Medium |
34916258
|
| 2011 |
Robo2 is required for maintenance of an anti-reflux mechanism at the ureterovesical junction; Robo2-deficient mice develop high-grade VUR due to a dilated and incompetent ureterovesical junction rather than ureteral obstruction; Robo2 is expressed around the developing ureterovesical junction. |
High-resolution micro-ultrasonography, microbubble contrast agent, ultrasound-guided aspiration, expression analysis, Robo2 KO mouse model |
PloS one |
Medium |
21949750
|
| 2020 |
Slit2-mediated growth cone collapse and axonal retraction are eliminated by Nox2 inhibition; slit2 increases growth cone hydrogen peroxide levels via Nox2 activation; astray/nox2 double heterozygotes show reduced retinotectal innervation, placing NADPH oxidase 2 downstream of slit2/Robo2 signaling. |
Zebrafish RGC culture, pharmacological Nox inhibition, Nox2 mutant fish, ROS biosensor imaging, growth cone collapse assay, astray/nox2 genetic interaction |
Developmental neurobiology |
Medium |
33191581
|
| 2021 |
Soluble TREM-1 (sTREM-1) is identified as a novel ligand for Robo2; sTREM-1 binds Robo2 on hepatic stellate cells and activates downstream Smad2/3 and PI3K/Akt signaling pathways, promoting HSC activation and liver fibrosis; HSC-specific knockdown of Robo2 inhibits sTREM-1-induced HSC activation. |
Pull-down assay with mass spectrometry (receptor identification), co-IP and immunofluorescence (interaction verification), Robo2 siRNA knockdown in LX-2 cells, AAV-mediated HSC-specific Robo2 knockdown in mouse fibrosis model |
Journal of cellular and molecular medicine |
Medium |
34750987
|
| 2021 |
The Slit-binding Ig1 domain of Drosophila Robo2 is required for midline repulsion, lateral axon pathway formation, and proper subcellular localization in embryonic neurons; removal of Ig1 from Robo2 (but not Robo1) disrupts axonal localization, suggesting a unique role for this domain in Robo2. |
CRISPR/Cas9-based endogenous gene replacement (robo2ΔIg1), in vivo axon guidance analysis, protein localization imaging |
Genesis |
Medium |
34411419
|
| 2020 |
ROBO2 expression in podocytes is upregulated after glomerular injury; loss of ROBO2 in podocytes (conditional KO) protects from foot process effacement and proteinuria after glomerular injury (protamine sulfate or nephrotoxic serum); overexpression of ROBO2 in cultured mouse podocytes compromises cell adhesion. |
Podocyte-specific Robo2 conditional KO, glomerular injury models (protamine sulfate, NTS), electron microscopy, proteinuria measurement, ROBO2 overexpression in cultured podocytes |
The American journal of pathology |
High |
32220420
|
| 2023 |
Robo2 conditional deletion in adult β cells causes loss of pancreatic islet architecture without affecting β cell identity or maturation, demonstrating that Robo2 actively maintains adult islet architecture rather than solely setting it during development. |
Adult conditional Robo2 deletion in β cells (inducible Cre), islet architecture quantification, β cell identity/maturation markers |
Developmental biology |
Medium |
37972678
|
| 2020 |
ROBO2 in the common nephric duct (CND) regulates CND migration and fusion with the primitive bladder via its novel binding partner RALDH2; delayed apoptosis due to failure of CND fusion in Robo2-/- embryos causes abnormal ureter connection; retinoic acid rescues ureter anomalies in Robo2-/- embryos. |
Robo2 knockout mouse, protein interaction studies (novel binding partner RALDH2), retinoic acid rescue experiment, apoptosis analysis |
Developmental biology |
Medium |
32562756
|
| 2013 |
Lhx2 transcription factor controls thalamocortical axon guidance and topographic sorting by regulating expression of Robo1 and Robo2 guidance receptors; augmenting Robo1 function restores normal axon guidance in Lhx2-overexpressing neurons, placing Lhx2 upstream of Robo1/Robo2 in thalamocortical circuit formation. |
Conditional deletion of Lhx2 in thalamus, Lhx2 overexpression, thalamocortical axon tracing, Robo1/Robo2 expression analysis, Robo1 rescue experiment |
The Journal of neuroscience |
Medium |
22457488
|
| 2009 |
Robo2 is required in Xenopus RGCs for dendrite branching but not guidance; Slit/Robo2 signaling stimulates dendrite branching via Robo2 (Robo3 has no effect on dendrites); in the same cells, both Robo2 and Robo3 function in concert in axons to mediate axonal guidance and respond to Slits, demonstrating distinct functions of the same receptor in axons versus dendrites. |
Antisense knockdown, dominant-negative Robo2/Robo3 constructs, in vitro Xenopus RGC cultures, dendrite and axon morphometry |
Mechanisms of development |
Medium |
19961927
|
| 2022 |
Robo2 and Gen1 coregulate ureteric budding by activating the GDNF/RET pathway and downstream MAPK/ERK signaling, promoting cell proliferation; double gene disruption (Robo2 + Gen1) significantly increases CAKUT phenotypes, and this is rescued by MAPK/ERK inhibitor U0126. |
Robo2/Gen1 double mutant mouse model (piggyBac transposon), MAPK/ERK pathway analysis, cell proliferation assay, U0126 pharmacological rescue |
Frontiers in medicine |
Medium |
35071283
|
| 2004 |
Drosophila robo2 and robo3 are necessary for serotonergic neuron differentiation, functioning independently of their ligand Slit; loss of robo2 or robo3 causes loss of serotonin transporter (SerT) expression and loss of eagle (eg) transcription factor expression in serotonergic neurons; robo2 and eg interact genetically to regulate SerT expression. |
Drosophila genetics, loss-of-function mutants, slit mutant comparison, genetic interaction (robo2;eg double mutant), SerT and Eg expression analysis |
Development (Cambridge, England) |
Medium |
14973268
|
| 2026 |
CD47 stabilizes ROBO2 protein by sequestering the E3 ubiquitin ligase ITCH, thereby blocking ubiquitination and proteasomal degradation of ROBO2; loss of CD47 leads to ROBO2 degradation, reducing GBM cell proliferation and migration. |
Co-immunoprecipitation (CD47-ITCH-ROBO2 complex), ubiquitination assay, proteasome inhibitor experiments, CD47 and ROBO2 loss-of-function in GBM cells, in vivo tumor burden assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
41871254
|
| 2025 |
Slit1b/2-Robo2 repulsive signaling in the amacrine cell layer is essential to initiate apical horizontal cell migration during retinal lamination; disruption of this pathway causes basal retention of horizontal cells. |
Zebrafish transcriptomics, targeted CRISPR screening, live imaging of horizontal cell migration |
bioRxivpreprint |
Medium |
bio_10.1101_2025.07.23.666134
|