Mullins Lab

Research Overview

We are studying the molecular mechanisms by which a BMP (Bone Morphogenetic Protein) signal transduction pathway establishes different aspects of the vertebrate body plan. Various zebrafish mutants of BMP pathway components, as well as antisense knockdown approaches are used to dissect the molecular mechanisms by which this pathway establishes different cell types. We are studying the formation, function, and temporal regulation of a BMP activity gradient, which is implicated in specification of diverse cell types along the dorsal-ventral axis. We have shown that this gradient is essential in neural crest specification and is linked to dorsal-ventral patterning of neural tissue. Moreover, a subset of our defined components also function in post-embryonic heart development. Misregulation of BMP signaling leads to a debilitating disease in humans called fibrodysplasia ossificans progressiva (FOP). We are currently trying to establish a model for FOP in the zebrafish.

Elaboration of the vertebrate body plan relies not only on zygotic processes, but also on maternally-controlled processes: that is, processes that depend on products derived from the mother that are deposited into the oocyte and are critical for proper development of the embryo. To this end, we performed a large-scale maternal-effect mutant screen, not previously performed in a vertebrate, to identify mutants of key genes specifically required in the mother for oocyte development, egg activation, fertilization, the mid-blastula transition, and establishment of the axes of the vertebrate embryo. We identified numerous mutants in these processes and are studying the molecular and cellular basis for the defects, including positional cloning of the mutated genes.