Our previous studies have identified megalin as a novel genetic factor that controls forebrain
development. Mutations in the Megalin gene cause Donnai-Barrow syndrome in patients. We
will characterize in detail the phenotype of megalin-deficient mouse and zebrafish models with
the ultimate aim of identifying the molecular mechanisms underlying early forebrain patterning
defects that lead to holoprosencephaly. Studies will focus on disturbed BMP4- and SHH-
signaling in megalin mutants, and how megalin interacts with these pathways. Insights from our
analyses of animal models and affected individuals will lead to a better understanding of
pathophysiologic pathways underlying Donnai-Barrow syndrome and forebrain midline defects.
|
