Roundabout homolog 1 is a protein that in humans is encoded by the ROBO1 gene. [5] [6] [7]
Roundabout homolog 1 is a protein that in humans is encoded by the ROBO1 gene. [5] [6] [7]
Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The protein encoded by ROBO1 is structurally similar to a Drosophila integral membrane protein which is encoded by the Drosophila roundabout gene (a member of the immunoglobulin gene superfamily) and is both an axon guidance receptor and a cell adhesion receptor, known to be involved in the decision by axons to cross the central nervous system midline. Two transcript variants encoding different isoforms have been found for ROBO1. [7]
ROBO1 was implicated in a communication disorder based on a Finnish pedigree with severe dyslexia. Analyses revealed a translocation had occurred disrupting ROBO1. [8] Study of the phonological memory component of the language acquisition system suggests that ROBO1 polymorphisms are associated with functioning in this system. [9] The gene is thought to be related to the brain's ability to represent quantities, and is correlated with better math scores of young children in one limited study. [10]
Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately is an area of ongoing research.
The floor plate is a structure integral to the developing nervous system of vertebrate organisms. Located on the ventral midline of the embryonic neural tube, the floor plate is a specialized glial structure that spans the anteroposterior axis from the midbrain to the tail regions. It has been shown that the floor plate is conserved among vertebrates, such as zebrafish and mice, with homologous structures in invertebrates such as the fruit fly Drosophila and the nematode C. elegans. Functionally, the structure serves as an organizer to ventralize tissues in the embryo as well as to guide neuronal positioning and differentiation along the dorsoventral axis of the neural tube.
Netrin receptor DCC, also known as DCC, or colorectal cancer suppressor is a protein which in humans is encoded by the DCC gene. DCC has long been implicated in colorectal cancer and its previous name was Deleted in colorectal carcinoma. Netrin receptor DCC is a single transmembrane receptor.
Cadherin EGF LAG seven-pass G-type receptor 1 also known as flamingo homolog 2 or cadherin family member 9 is a protein that in humans is encoded by the CELSR1 gene.
Protein patched homolog 1 is a protein that is the member of the patched family and in humans is encoded by the PTCH1 gene.
Slit homolog 2 protein is a protein that in humans is encoded by the SLIT2 gene.
Mannose-6-phosphate receptor binding protein 1 (M6PRBP1) is a protein which in humans is encoded by the M6PRBP1 gene. Its gene product, as well as the gene itself, is commonly known as TIP47.
Ephrin-A2 is a protein that in humans is encoded by the EFNA2 gene.
Ephrin-B3 is a protein that in humans is encoded by the EFNB3 gene.
Netrin-1 is a protein that in humans is encoded by the NTN1 gene.
Roundabout homolog 2 is a protein that in humans is encoded by the ROBO2 gene.
Plexin-A2 is a protein that in humans is coded by the PLXNA2 gene.
Roundabout homolog 3 is a protein that in humans is encoded by the ROBO3 gene.
Splicing factor 45 is a protein that in humans is encoded by the RBM17 gene.
SLIT-ROBO Rho GTPase-activating protein 1 is an enzyme that in humans is encoded by the SRGAP1 gene.
The Roundabout (Robo) family of proteins are single-pass transmembrane receptors that are highly conserved across many branches of the animal kingdom, from C. elegans to humans. They were first discovered in Drosophila, through a mutant screen for genes involved in axon guidance. The Drosophila roundabout mutant was named after its phenotype, which resembled the circular traffic junctions. The Robo receptors are most well known for their role in the development of the nervous system, where they have been shown to respond to secreted Slit ligands. One well-studied example is the requirement for Slit-Robo signaling in regulation of axonal midline crossing. Slit-Robo signaling is also critical for many neurodevelopmental processes including formation of the olfactory tract, the optic nerve, and motor axon fasciculation. In addition, Slit-Robo signaling contributes to cell migration and the development of other tissues such as the lung, kidney, liver, muscle and breast. Mutations in Robo genes have been linked to multiple neurodevelopmental disorders in humans.
Slit is a family of secreted extracellular matrix proteins which play an important signalling role in the neural development of most bilaterians. While lower animal species, including insects and nematode worms, possess a single Slit gene, humans, mice and other vertebrates possess three Slit homologs: Slit1, Slit2 and Slit3. Human Slits have been shown to be involved in certain pathological conditions, such as cancer and inflammation.
Slit-Robo is the name of a cell signaling protein complex with many diverse functions including axon guidance and angiogenesis.
The growth cone is a highly dynamic structure of the developing neuron, changing directionality in response to different secreted and contact-dependent guidance cues; it navigates through the developing nervous system in search of its target. The migration of the growth cone is mediated through the interaction of numerous trophic and tropic factors; netrins, slits, ephrins and semaphorins are four well-studied tropic cues (Fig.1). The growth cone is capable of modifying its sensitivity to these guidance molecules as it migrates to its target; this sensitivity regulation is an important theme seen throughout development.
Alain Chédotal is a French researcher specialising in the development of neural circuits. He has been a member of the French Academy of sciences since 2017.
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