During the development of the cerebral cortex, the radial glia give rise to neurons, which migrate into the upper layers of the cortex. Proliferation, differentiation and migration are processes that must be tightly regulated. Morphogens are extracellular proteins that act at several stages of these processes, but their dynamics and precise molecular pathways are not always clear. In particular, how cells can change their responses to a single morphogen during development is a central and still open question. By studying single-cell RNA-seq data, we discovered that the expression of specific glypicans (Gpc) appears to be associated with different stages of cortical development and different types of signaling pathways, including Sonic Hedgehog (Shh), a morphogen essential for neuronal development. Furthermore, our preliminary data show that manipulation of Gpc gene expression levels in the embryonic brain differentially affects cell distribution in cortical layers. Thus, we hypothesize that each specific Gpc is closely associated with a certain type of cellular response. In this project, we aim to 1/ characterize Gpc-Shh interactions using biophysical and structural approaches and 2/ identify how distinct Gpc differentially regulate specific processes, such as differentiation, neuronal migration and morphogenic responses, in the developing cortex. Overall, the GLYPHH project will identify the molecular code that triggers specific Shh signaling and provide new insights into the roles of specific glypicans in the developing brain. Finally, this study will have an impact on several fields such as glycobiology, neuronal development and cancerology.