PT  - JOURNAL ARTICLE
AU  - Rodríguez-Prieto, Ángela
AU  - Mateos-White, Isabel
AU  - Aníbal-Martínez, Mar
AU  - Navarro-González, Carmen
AU  - Gil-Sanz, Cristina
AU  - Domínguez-Canterla, Yaiza
AU  - González-Manteiga, Ana
AU  - Del Buey Furió, Verónica
AU  - López-Bendito, Guillermina
AU  - Fazzari, Pietro
TI  - Nrg1 intracellular signaling regulates the development of interhemispheric callosal axons in mice
AID  - 10.26508/lsa.202302250
DP  - 2024 Sep 01
TA  - Life Science Alliance
PG  - e202302250
VI  - 7
IP  - 9
4099  - http://www.life-science-alliance.org/content/7/9/e202302250.short
4100  - http://www.life-science-alliance.org/content/7/9/e202302250.full
SO  - Life Sci. Alliance2024 Sep 01; 7
AB  - Schizophrenia is associated with altered cortical circuitry. Although the schizophrenia risk gene NRG1 is known to affect the wiring of inhibitory interneurons, its role in excitatory neurons and axonal development is unclear. Here, we investigated the role of Nrg1 in the development of the corpus callosum, the major interhemispheric connection formed by cortical excitatory neurons. We found that deletion of Nrg1 impaired callosal axon development in vivo. Experiments in vitro and in vivo demonstrated that Nrg1 is cell-autonomously required for axonal outgrowth and that intracellular signaling of Nrg1 is sufficient to promote axonal development in cortical neurons and specifically in callosal axons. Furthermore, our data suggest that Nrg1 signaling regulates the expression of Growth Associated Protein 43, a key regulator of axonal growth. In conclusion, our study demonstrates that NRG1 is involved in the formation of interhemispheric callosal connections and provides a novel perspective on the relevance of NRG1 in excitatory neurons and in the etiology of schizophrenia.All reagents and additional information about the results and methodology are available upon request.