Helen McBride, Ph.D.
Alumnus of the BIC
was senior research fellow
Helen is now at Amgen.
Go to Helen's website
My research interests focus on understanding how the enteric nervous system (ENS) is formed and patterned properly during development. The intrinsic enteric nervous system forms from one cell type, the neural crest. What does that really mean? It means that one group of cells derived from the same location in the embryo gives rise to millions of neurons and glial (support) cells within the adult ENS. And those neurons more resemble the complexity seen in the brain than in the rest of the peripheral nervous system. That is why the ENS is often called the "little brain".
Neural crest cells migrate into the developing gut tissue from the neural tube early in development and proceed to colonize the entire length of the gut tract. This is no small feat given that the gut is growing while these cells are migrating through it to reach the "end". While migrating, there is a careful balance between proliferation and differentiation to ensure that there are enough cells around to make it to the end of this long journey.
Once neural crest cells have stopped migrating and begin the process of differentiation into the cell types they will become in the adult a new set of challenges emerges. How do they decide who becomes a neuron and who becomes a glial cell? Balancing the right number of neurons and support cells is critical to the later growth of the ENS. Getting it wrong may lead to problems in function later on.
Once these cells have decided to become neurons, a new set of choices begins. What type of neuron to become? There are over ten choices and these must be chosen correctly depending on what section of the gut the neural crest cell finds herself in. Getting it right ensures proper peristalsis; getting it wrong may lead to chronic constipation or obstruction.
How am I approaching these questions? I have chosen a variety of imaging methods to address how neural crest cells migrate within the developing gut and later, how motility emerges in the adult ENS. By developing an assay for neural crest migration in the embryonic gut, I can test candidate molecules for their role in ENS formation in the intact tissue. Using uMRI in adult animals allows me to similarly screen through candidate mouse lines for mutations that affect motility in subtle ways. In addition, I am studying how signaling molecules pattern the underlying gut tissue that neural crest cells migrate through. Because communication between neural crest cells and the gut should be important in properly patterning the ENS, molecules that are identified from these studies will then be tested in the migration assay. Synergy between these three areas of interest will lead to a continuing stream of signaling molecules to study at multiple levels of gut and ENS development and will, I hope, answer some of the fascinating and very basic questions listed above.
recent publications:
Wnt family gene expression in the developing chicken gut
Surface Imaging Microscopy (SIM)
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