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Trio GEF mediates RhoA activation downstream of Slit2 and coordinates telencephalic wiring.
- Source :
-
Development (Cambridge, England) [Development] 2018 Oct 02; Vol. 145 (19). Date of Electronic Publication: 2018 Oct 02. - Publication Year :
- 2018
-
Abstract
- Trio, a member of the Dbl family of guanine nucleotide exchange factors, activates Rac1 downstream of netrin 1/DCC signalling in axon outgrowth and guidance. Although it has been proposed that Trio also activates RhoA, the putative upstream factors remain unknown. Here, we show that Slit2 induces Trio-dependent RhoA activation, revealing a crosstalk between Slit and Trio/RhoA signalling. Consistently, we found that RhoA activity is hindered in vivo in T rio mutant mouse embryos. We next studied the development of the ventral telencephalon and thalamocortical axons, which have been previously shown to be controlled by Slit2. Remarkably, this analysis revealed that Trio knockout (KO) mice show phenotypes that bear strong similarities to the ones that have been reported in Slit2 KO mice in both guidepost corridor cells and thalamocortical axon pathfinding in the ventral telencephalon. Taken together, our results show that Trio induces RhoA activation downstream of Slit2, and support a functional role in ensuring the proper positioning of both guidepost cells and a major axonal tract. Our study indicates a novel role for Trio in Slit2 signalling and forebrain wiring, highlighting its role in multiple guidance pathways as well as in biological functions of importance for a factor involved in human brain disorders.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2018. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Axon Guidance
Axons metabolism
Embryo, Mammalian cytology
Fibroblasts metabolism
Gene Expression Regulation, Developmental
Growth Cones metabolism
Guanine Nucleotide Exchange Factors genetics
Intercellular Signaling Peptides and Proteins genetics
Mice, Knockout
Models, Biological
Nerve Tissue Proteins genetics
Neurons metabolism
Phosphoproteins genetics
Protein Serine-Threonine Kinases genetics
RNA, Messenger genetics
RNA, Messenger metabolism
Thalamus embryology
Thalamus metabolism
Body Patterning
Guanine Nucleotide Exchange Factors metabolism
Intercellular Signaling Peptides and Proteins metabolism
Nerve Tissue Proteins metabolism
Phosphoproteins metabolism
Protein Serine-Threonine Kinases metabolism
Telencephalon embryology
Telencephalon metabolism
rhoA GTP-Binding Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 145
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 30177526
- Full Text :
- https://doi.org/10.1242/dev.153692