Le Ma Research

The research in the Ma laboratory focuses on nerve branching, a key step in establishing synaptic connection during neural circuit development.  Nerve branches are associated with axons and dendrites and seen in almost every nerve cell, yet the mechanisms underlying their formation is not well understood.  How do branches form at the right time and in the right place?  How do they establish specific size and pattern?   How are they determined by genetic programs and influenced by environmental factors?  How do they remodel in response to experience or injury?  How are they affected in neurological disease, and how do they contribute to developmental disorders?  To explore these fundamental questions, the laboratory employs modern molecular, genetic and cell biological tools and studies the development nerve branching in dorsal root sensory neurons and cerebellar Purkinje cells.

Using mammalian neuronal cell models, we investigate known factors in controlling stereotypic branched patterns and search new genes that are critical to regulating different aspects of branching.  A variety of modern molecular techniques are combined with primary cell culture and in vivo analysis in these studies.  For examples, a) following sensory neurons in the dorsal root ganglion (DRG) during early development, we have identified two signaling mechanisms that are required for proper bifurcation; and b) using a viral delivery technique to inactivate gene function while simultaneously visualizing single cell morphology, we have identified a cell surface signaling system required for cerebellar Purkinje cell dendrite self-avoidance, a patterning mechanism generating elaborated branches that rarely overlap.  

Although branched morphologies come in different shape and size, only a limited number of factors are encoded by the genome.  To understand how different branching patterns are generated by a combination of environmental cues and genetic programs, we investigate the cooperation of molecules that regulates different steps of branching, including initiation, growth, guidance, stabilization, and patterning.  Cutting-edge cell biological tools including live cell imaging are employed for these studies.  Recently, we developed a novel computer vision method that allows us to rapidly analyze microtubule assembly and regulation in neurons.

Branching morphogenesis is critical to generating complex neural networks, but what is the physiological consequence when branching regulation is perturbed?  How are they affected in neurological and psychiatric diseases?  Knowledge of molecular pathways coupled to the structurally robust phenotypes offers us a unique opportunity to investigate the contribution of nerve branching to normal circuit functions.  In addition, we are interested in the response of nerve branches to degeneration and their regenerative potentials after injury.