Mechanisms Regulating Forebrain Development
Regional patterning is known to occur through the action of morphogens. Morphogens are defined as secreted signaling molecules that act in a gradient and at a distance from the source of the morphogen. One of the biggest puzzles in developmental biology is how do morphogens travel across several cell diameters and form gradients. Our lab has been using a variety of molecular and biochemical tools to show that the N-lipid and C-lipids of the sonic hedgehog (Shh) morphogen are critical to the formation of a multimeric complex that is involved in a novel morphogenic mechanism. Another focus of the lab is the study of a novel ventral forebrain non-coding RNA that is involved in transcriptionally activating homeodomain expression in the ventral forebrain. This is the first demonstration that developmentally regulated non-coding RNAs can cooperate with homeodomain proteins to activate specific enhancers. Thesis projects include the construction of mouse models to test the role of the Shh multimers in morphogenesis in vivo, as well as the role of the novel non-coding RNAs in cis and trans in activating specific homeodomain expression in vivo.