Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain
Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2016-03-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/5/3/336 |
| _version_ | 1818859691636162560 |
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| author | Niurka Trujillo-Paredes Concepción Valencia Gilda Guerrero-Flores Dulce-María Arzate José-Manuel Baizabal Magdalena Guerra-Crespo Ayari Fuentes-Hernández Iván Zea-Armenta Luis Covarrubias |
| author_facet | Niurka Trujillo-Paredes Concepción Valencia Gilda Guerrero-Flores Dulce-María Arzate José-Manuel Baizabal Magdalena Guerra-Crespo Ayari Fuentes-Hernández Iván Zea-Armenta Luis Covarrubias |
| author_sort | Niurka Trujillo-Paredes |
| collection | DOAJ |
| description | Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs), but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor. Coupling between neurogenesis and dopaminergic differentiation was indicated from the coincident emergence of neuronal and dopaminergic markers. Early in differentiation, decreasing Notch signalling caused a reduction in NPCs and an increase in dopaminergic neurons in association with dynamic changes in the proportion of sequentially-linked dopaminergic NPCs (Msx1/2+, Ngn2+, Nurr1+). These effects in differentiation caused a significant reduction in the number of dopaminergic neurons produced. Accordingly, Dll1 haploinsufficient adult mice, in comparison with their wild-type littermates, have a consistent reduction in neuronal density that was particularly evident in the substantia nigra pars compacta. Our results are in agreement with a mathematical model based on a Dll1-mediated regulatory feedback loop between early progenitors and their dividing precursors that controls the emergence and number of dopaminergic neurons. |
| first_indexed | 2024-12-19T09:16:13Z |
| format | Article |
| id | doaj.art-487be002063045e3b2c4ac1f3347d69d |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T09:16:13Z |
| publishDate | 2016-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-487be002063045e3b2c4ac1f3347d69d2022-12-21T20:28:05ZengThe Company of BiologistsBiology Open2046-63902016-03-015333634710.1242/bio.013383013383Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brainNiurka Trujillo-Paredes0Concepción Valencia1Gilda Guerrero-Flores2Dulce-María Arzate3José-Manuel Baizabal4Magdalena Guerra-Crespo5Ayari Fuentes-Hernández6Iván Zea-Armenta7Luis Covarrubias8 Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Cuernavaca, Morelos 62210, México Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Cuernavaca, Morelos 62210, México Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Cuernavaca, Morelos 62210, México Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Cuernavaca, Morelos 62210, México Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Cuernavaca, Morelos 62210, México Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Coyoacán, Ciudad de México 04510, México Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Cuernavaca, Morelos 62210, México Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs), but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor. Coupling between neurogenesis and dopaminergic differentiation was indicated from the coincident emergence of neuronal and dopaminergic markers. Early in differentiation, decreasing Notch signalling caused a reduction in NPCs and an increase in dopaminergic neurons in association with dynamic changes in the proportion of sequentially-linked dopaminergic NPCs (Msx1/2+, Ngn2+, Nurr1+). These effects in differentiation caused a significant reduction in the number of dopaminergic neurons produced. Accordingly, Dll1 haploinsufficient adult mice, in comparison with their wild-type littermates, have a consistent reduction in neuronal density that was particularly evident in the substantia nigra pars compacta. Our results are in agreement with a mathematical model based on a Dll1-mediated regulatory feedback loop between early progenitors and their dividing precursors that controls the emergence and number of dopaminergic neurons.http://bio.biologists.org/content/5/3/336Delta-like 1NotchNeurogenesisDopaminergic neurons |
| spellingShingle | Niurka Trujillo-Paredes Concepción Valencia Gilda Guerrero-Flores Dulce-María Arzate José-Manuel Baizabal Magdalena Guerra-Crespo Ayari Fuentes-Hernández Iván Zea-Armenta Luis Covarrubias Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain Biology Open Delta-like 1 Notch Neurogenesis Dopaminergic neurons |
| title | Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain |
| title_full | Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain |
| title_fullStr | Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain |
| title_full_unstemmed | Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain |
| title_short | Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain |
| title_sort | regulation of differentiation flux by notch signalling influences the number of dopaminergic neurons in the adult brain |
| topic | Delta-like 1 Notch Neurogenesis Dopaminergic neurons |
| url | http://bio.biologists.org/content/5/3/336 |
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