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Table of contents
LIST OF ILLUSTRATIONS
INTRODUCTION
I. Homeoproteins
A. Homeoproteins as classical transcription factors
B. Homeoproteins Otx1 and Otx2 and their roles in brain and eye development
C. Homeoproteins unconventional intercellular transfer
D. Homeoproteins as signaling proteins with in vivo roles
II. Glycosaminoglycan
A. Glycosaminoglycan structures
B. Glycosaminoglycan biosynthesis
C. Glycosaminoglycan interaction with morphogens and growth factors
D. Glycosaminoglycans in the postnatal brain
III. Critical period plasticity
A. Critical periods
B. Cellular and molecular mechanisms of cortical plasticity
C. Reopening plasticity in the adult
IV. Otx2 homeoprotein and visual cortex plasticity
A. Otx2 transfer in the visual cortex during the critical period
B. Otx2 transfer in the adult consolidated visual cortex
MATERIALS AND METHODS
I. Plasmid and proteins
II. Animals
III. Cell culture
IV. Animal experiments
V. Cerebrospinal fluid sampling
VI. Cell surface biotinylation
VII. Western blot
VIII. RNA extraction and deep sequencing
IX. Immunohistochemistry
X. Glycosaminoglycan experiments
XI. Statistical analysis
RESULTS AND DISCUSSION
I. Otx2 transgenic mice to investigate Otx2 transfer roles in the visual system
A. Otx2-AA protein activity
B. Otx2 activity in eye development and maintenance
C. Otx2 GAG-binding motif has a role in critical period timing
D. Towards the identification of targets of Otx2 in the visual cortex
Discussion
II. Identifying Otx2-binding GAGs
A. Otx2-binding GAGs in the cortex
B. GAG-binding homeoproteins: Engrailed2 versus Otx2
Discussion
III. Tools for disrupting Otx2 transfer in the visual cortex
A. A synthetic CS-E hexasaccharide interferes with Ox2 cortical transfer
B. Blocking Otx2 transfer in vivo in a single chain antibody mouse
Discussion
CONCLUSION AND PERSPECTIVES
I. Otx2, a master regulator of cortical plasticity?
II. Otx2-GAG interaction, from the source to the cortex?
REFERENCES
