The role of the transcription factor zic2 as a determinant of axonal laterality in the spinal cord
- Autores: Augusto Escalante Rodríguez
- Directores de la Tesis: Eloísa Herrera González (dir. tes.)
- Lectura: En la Universidad Miguel Hernández de Elche ( España ) en 2013
- Idioma: español
- Tribunal Calificador de la Tesis: Paola Bovolenta Nicolao (presid.), Fernando Moya Rodríguez (secret.), Miguel Angel Valdeolmillos López (voc.), Avihu Klar (voc.), Ana Carmena de la Cruz (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: RediUMH
- Resumen
In bilaterally symmetric organisms, interhemispheric communication is essential for sensory processing and motor coordination. Failure in the proper wiring of bilateral circuits leads to the formation of aberrant connections between different parts of the nervous system which causes their malfunctions and negatively affects survival of the animal.
The mechanisms that govern axon midline crossing during development have been well-studied, particularly at the spinal cord. However, the molecular program that determines axonal ipsilaterality remains poorly understood, specially at the transcriptional level. Very little is known about the role of transcription factors in the establishment of contra- versus ipsilateral projections.
Here, we demonstrate that ipsilateral neurons whose axons grow in close proximity to the midline, such as the ascending dorsospinal tracts, avoid midline crossing because they transiently activate the transcription factor Zic2. In contrast, uncrossed neurons whose axons never approach to the midline control axonal laterality by Zic2-independent mechanisms. Zic2 induces EphA4 expression in dorsospinal neurons to prevent midline crossing while Robo3 is downregulated to ensure that axons enter the dorsal tracts instead of growing ventrally. Together with previous reports, our data reveal a critical role for Zic2 as a determinant of axon midline avoidance in the CNS across species and pathways.
