Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons
The fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organi...
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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.682067/full |
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| author | Verónica Company Abraham Andreu-Cervera M. Pilar Madrigal Belén Andrés Francisca Almagro-García Alain Chédotal Guillermina López-Bendito Salvador Martinez Diego Echevarría Juan A. Moreno-Bravo Eduardo Puelles |
| author_facet | Verónica Company Abraham Andreu-Cervera M. Pilar Madrigal Belén Andrés Francisca Almagro-García Alain Chédotal Guillermina López-Bendito Salvador Martinez Diego Echevarría Juan A. Moreno-Bravo Eduardo Puelles |
| author_sort | Verónica Company |
| collection | DOAJ |
| description | The fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organization of habenular circuitry requires complex molecular programs to control the wiring of the habenula during development. However, the mechanisms guiding the habenular axons toward their targets remain mostly unknown. Here, we demonstrate the role of the mesodiencephalic dopaminergic neurons (substantia nigra pars compacta and ventral tegmental area) as an intermediate target for the correct medial habenular axons navigation along the anteroposterior axis. These neuronal populations are distributed along the anteroposterior trajectory of these axons in the mesodiencephalic basal plate. Using in vitro and in vivo experiments, we determined that this navigation is the result of netrin 1 attraction generated by the mesodiencephalic dopaminergic neurons. This attraction is mediated by the receptor deleted in colorectal cancer (DCC), which is strongly expressed in the medial habenular axons. The increment in our knowledge on the fasciculus retroflexus trajectory guidance mechanisms opens the possibility of analyzing if its alteration in mental health patients could account for some of their symptoms. |
| first_indexed | 2024-12-17T05:05:58Z |
| format | Article |
| id | doaj.art-5051c43a63e247758038aac1cd3dbef1 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-17T05:05:58Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-5051c43a63e247758038aac1cd3dbef12022-12-21T22:02:25ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.682067682067Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular AxonsVerónica Company0Abraham Andreu-Cervera1M. Pilar Madrigal2Belén Andrés3Francisca Almagro-García4Alain Chédotal5Guillermina López-Bendito6Salvador Martinez7Diego Echevarría8Juan A. Moreno-Bravo9Eduardo Puelles10Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainSorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, SpainThe fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organization of habenular circuitry requires complex molecular programs to control the wiring of the habenula during development. However, the mechanisms guiding the habenular axons toward their targets remain mostly unknown. Here, we demonstrate the role of the mesodiencephalic dopaminergic neurons (substantia nigra pars compacta and ventral tegmental area) as an intermediate target for the correct medial habenular axons navigation along the anteroposterior axis. These neuronal populations are distributed along the anteroposterior trajectory of these axons in the mesodiencephalic basal plate. Using in vitro and in vivo experiments, we determined that this navigation is the result of netrin 1 attraction generated by the mesodiencephalic dopaminergic neurons. This attraction is mediated by the receptor deleted in colorectal cancer (DCC), which is strongly expressed in the medial habenular axons. The increment in our knowledge on the fasciculus retroflexus trajectory guidance mechanisms opens the possibility of analyzing if its alteration in mental health patients could account for some of their symptoms.https://www.frontiersin.org/articles/10.3389/fcell.2021.682067/fullhabenulafasciculus retroflexusnetrin 1DCCaxon guidancesubstantia nigra pars compacta |
| spellingShingle | Verónica Company Abraham Andreu-Cervera M. Pilar Madrigal Belén Andrés Francisca Almagro-García Alain Chédotal Guillermina López-Bendito Salvador Martinez Diego Echevarría Juan A. Moreno-Bravo Eduardo Puelles Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons Frontiers in Cell and Developmental Biology habenula fasciculus retroflexus netrin 1 DCC axon guidance substantia nigra pars compacta |
| title | Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons |
| title_full | Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons |
| title_fullStr | Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons |
| title_full_unstemmed | Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons |
| title_short | Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons |
| title_sort | netrin 1 mediated role of the substantia nigra pars compacta and ventral tegmental area in the guidance of the medial habenular axons |
| topic | habenula fasciculus retroflexus netrin 1 DCC axon guidance substantia nigra pars compacta |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.682067/full |
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