User:Kaleinonen

Proposal

Wikipedia Article Proposal/Plan Lindsey Boucher, Duncan Cleveland, Kailee Leinonen

The categories we intend to discuss in the Wiki article are as follows: function, location/structure, associations with other molecules (likely the SLIT ligands that they associate and form complexes with), and clinical applications. We potentially may also have a small section of the conservation of the Robo gene family across species, as well as including the homologus of Robo genes in various species.#

Introduction/Overview (All will contribute)

- For the introduction section, each of us will expand upon the existing introduction section, discussing the Robo gene family as a whole. The introduction will contain the basic details of function, location, structure, associations with Slit, and clinical applications.

Function of Robo genes (Kailee)

- The Robo gene family is thought to aid in the guidance of neurons as they are growing and extending throughout development by acting as a repulsive guidance receptor. Robo gene products are found to have a high affinity for Slit proteins, which have been proposed as the ligand for the Robo receptors. The Slit/Robo complexes have been observed in cell cultures to repel embryonic spinal neurons, suggesting that these complexes play some role in the development of the branching extensions of the nervous system.# -Robo genes have been shown to work in a variety of regions within the body, including in the formation of reproductive organs, blood vessels, and the hearts in Drosophila. They appear to be used mostly in the development phase of these structures within the embryos of the fetus. - Robo1 is - repulsive guidance receptor# - tumor suppressor/ - The Robo genes may act as tumor suppressors# - Robo2 - controls the extension of commissural axons away from the floor plate in the contralateral neural tube -Axonal guidance -Tumor suppressor -Robo 3 -Highly stimulated prior to the axon crossing the midline (moving from one part of the nervous system to the other. -Failure to cross the midline results in horizontal gaze palsy with progressive scoliosis -Most likely expressed in the hindbrain, as shown through in situ studies -Promotes transition of neurons into S phase -Robo4 -Little is known -Stabilize vascular tissue, may inhibit growth of blood vessels in mice

Location/Structure of Robo Genes (Lindsey)

- Robo1 - Robo1 is found on chormosome 3p12. Structurally, spanning 240 kb of genomic data, Robo1 has 29 exons. The Robo1 gene has been found to display many gene products through alternative splicing, helping to account for the various functions that these gene products exhibit.# - Robo1: Found within gliomas in high concentrations. Potential target concerning treatment and prevention of gliomas.# - Robo1 homologous to C. elegans sax3# - Robo2 -Chromosome 3 in humans and chromosome 16 in mice -Contains at least 27 exons -2 alternative first exons and 2 alternative promoters -Robo3 -Expressed in hindbrain -Contains 28 exons in humans with approximately 16,000 bases -Chromosome 11 -Robo4: Contains 18 exons, expressed on chromosome 11q24.2

Association of Robo with Slit (Duncan)

- Robo1 - SLIT2/Robo1 is a ligand receptor duo that has major effects on the distribution, migration, axon guidance, and branching of neuron cells. Both SLIT2 and Robo1 are found in varying concentrations in several types of brain tumors. SLIT2 is found in low concentrations in a variety of tumors, including astrocytomas, fillbrillary astrocytomas and glioblastomas. Robo1 is found within gliomas in high concentrations in numerous forms, including mRNA and as a protein. The SLIT2/Robo1 complex is thought to have multiple roles in the process of tumor suppression, though most mechanisms are unknown at this point. However, it has been proven that the SLIT2/Robo1 complex plays a role in the inhibition of glioma signaling and migration by inactivation of Cdc42-GTP.# - Robo2 - Encodes a transmembrane receptor for SLIT ligand -SLIT2/ROBO2 signaling restricts the extent of the glial cell-derived neurotrophic factor (GDNF) expression domain -Robo4 -Activated by SLIT2, when activated, inhibits angiogenesis (growth of new blood vessels)

Clinical Applications (All will likely contribute)

- Robo genes may have several important linkages to a variety of clinical applications. Robo genes may function as a tumor suppressor genes. A mutation within the Robo gene may also be cause a predisposition to dyslexia. -Mutations in Robo3 genes have been linked to Horizontal gaze palsy with progressive scoliosis (HGPPS), a disorder increasing curvature of the spine and decreasing vision. Patients with HGPPS have fixed horizontal eye movement in the sockets, meaning they must turn their head to see from side to side. -Robo 4 genes may have medical applications in diseases with enhanced angiogenesis and blood vessel growth.

Sources

Websites

http://omim.org/entry/602431#reference8 http://www.sciencedirect.com/science/article/pii/S153458070400108X http://www.genecards.org/cgi-bin/carddisp.pl?gene=ROBO1 http://www.ncbi.nlm.nih.gov/pubmed/21113198 http://omim.org/entry/602430?search=Roundabout%20gene%201&highlight=1%20gene%20roundabout http://www.ncbi.nlm.nih.gov/pubmed/10102268 http://omim.org/entry/602430?search=Roundabout%20gene%201&highlight=1%20gene%20roundabout http://ghr.nlm.nih.gov/condition/horizontal-gaze-palsy-with-progressive-scoliosis - Explanation of HGPPS, Robo3’s role in causing condition http://omim.org/entry/608630 - Robo3 Omin page http://omim.org/entry/607528 - Robo4 Omin page

Papers

Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance.Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, Tessier-Lavigne M, Kidd T.

Slit2/Robo1 signaling in gliomal migration and invasion. Xu et al.

Midline axon guidance and human genetic disorders. Izzi and Charron

Breakthroughs in the search for dyslexia candidate gene. McGrath et al.

Axon guidance: men and mice need rig and robo. Guthrie.

Axon guidance: Robos make the rules. Guthrie

Axon guidance: starting and stopping with Slit. Guthrie.

Potential role of the Slit/Robo signal pathway in angiogenesis- Fujiwara et al.

Integrins are required for cardioblast polarisation in Drosophila - Vanderploeg et al.

The SLIT/ROBO pathway: a regulator of cell function with implications for the reproductive system - Dickinson and Duncan