AUTHOR=Callejas-Marin Antuca , Moreno-Bravo Juan Antonio , Company Verónica , Madrigal M. Pilar , Almagro-García Francisca , Martínez Salvador , Puelles Eduardo 

TITLE=Gli2-Mediated Shh Signaling Is Required for Thalamocortical Projection Guidance

JOURNAL=Frontiers in Neuroanatomy

VOLUME=Volume 16 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2022.830758

DOI=10.3389/fnana.2022.830758

ISSN=1662-5129

ABSTRACT=The thalamocortical projections constitute one of the most prominent higher-level processing connections in the vertebrates and follow a highly stereotyped pathway from their origin in the thalamus to the cerebral cortex. Its functional complexity is the consequence not only of an extremely elaborate process of axon guidance but of activity dependent mechanisms. Gli2 is an intermediary transcription factor in the Sonic hedgehog (Shh) pathway. During neural early development, Shh has an important role in dorso-ventral patterning, diencephalic antero-posterior patterning and many later developmental processes, such as axon guidance and cell migration. Using a Gli2 knockout mouse line, we have studied the role of Shh signaling mediated by Gli2 in the development of the thalamocortical projections during embryonic development. In wild type brains, we have described the normal trajectory of the thalamocortical axons into the context of the prosomeric model. Then, we have compared it with the altered thalamocortical axons course in Gli2 homozygous embryos. The thalamocortical axons followed different trajectories and were misdirected to other territories due to alterations in the Robo/Slit signaling mechanism. In conclusion, the alteration of Gli2 mediated Shh signaling produces an erroneous specification of several territories related with the thalamocortical axons. This is translated into a huge modification in the pathfinding signaling mechanisms needed for the correct wiring of the thalamocortical axons.