Le Ma

Assistant Professor
Cell and Neurobiology
Zilkha Neurogenetic Institute
Keck School of Medicine

Research Topics

1. Molecular mechanisms of branching morphogenesis
2. Live imaging of axon growth, guidance and branching
3. Development and regeneration of neural networks

Research Overview

Much like the computer, our brain relies on electrical circuits for all the functions. However, unlike the computer, the neural circuits are assembled from billions of nerve cells, each making thousands of synaptic connections through axons and dendrites, the long and thin extensions from the cell body. In addition, these connections are established during embryonic development and any misregulation could lead to early childhood diseases such as mental retardation. Furthermore, many axonal and dendritic connections can be remodeled even after the circuits are established, yet such ability appears to be diminished over time in the central nervous system, contributing to the great medical challenge in adult nerve regeneration.

The research in my laboratory attempts to understand the general principles underlying neurite growth, guidance and branching, three key steps in establishing synaptic connection during development. Our current effort devotes to the understanding of branching, a process that is common to almost every nerve cell yet the mechanism of which is not well understood. How does the neuron decide when and where to make branches? What controls the branch number and pattern? How is it regulated coordinately with neurite growth and guidance to produce many striking cell morphologies in the brain? How are they modified by neuronal activities? To explore these questions, we use vertebrate sensory neurons in the dorsal root ganglion as a model and study their branch formation by combining a variety of approaches, including transgenic mice, primary cell culture and live cell imaging.

Using these modern tools, we recently discovered that the secreted molecule Slit and its cell surface receptor Robo play an important role in regulating arborization and bifurcation, two forms of branching of sensory neurons at different embryonic stages. This opens the door to further identifying the signaling network and studying the branching machinery inside the cell. In addition, it provides us a unique opportunity to understand the interplay between branching and neurite growth and guidance, two steps that are intimately associated with branching. We hope that our research on developing sensory neurons will not only help us uncover the wiring mechanisms of the nervous system, but also provide insights into regenerating adult neurons after injury.