Department of Genetics, HMSHarvard Medical School
Division of Genetics, Children's Hospital Boston
Center for Life Sciences 14047
3 Blackfan Circle
Boston, MA 02115
Like gears in a piece of clockwork, cells must fit together precisely to give rise to a functioning organ. Nowhere is this more apparent than in the human brain, where 100 billion neurons and 100 billion glia come together, each acquiring the necessary shapes and cell contacts to ultimately manufacture human consciousness. We want to understand the basic principles underlying how cell shape and cell-cell contacts are specified. For this purpose, we have turned to a set of 302 neurons with a highly predictable anatomy – the simple nervous system of the nematode C. elegans.
From the moment of fertilization in C. elegans, every cell division, cell migration, and cell shape change occurs almost identically in every individual, giving rise to worms that are nearly superimposable with one another. This is a tremendous advantage when trying to understand how cells form organs: in this system, they do it the same way every time. Additionally, they do it quickly – most morphogenesis takes place in a two-hour window in embryogenesis – and, because the embryos are transparent, every cell movement and cell shape change can be directly observed.
We have focused on the amphid, the major sense organ of C. elegans, consisting of 12 sensory neurons and two glia, all with stereotyped morphology. The neurons extend unbranched dendrites to the tip of the nose, a distance of 100 µm in adults, where they collect information about the environment. We asked the simple question, how do neurons know how long to make these dendrites? We showed the neurons are born at the nose, anchor there, and then the cell bodies crawl away, stretching the dendrites out behind them as they go. The anchoring is done by a pair of proteins similar to ones involved in sperm-egg adhesion, which are probably forming a local extracellular matrix to which neurons specifically anchor. We are now trying to understand what this anchor looks like and how it works. We are also asking how anchors at other sites might establish distinct adhesion sites for different classes of sensory neurons.
Ultimately, our goal is to define the mechanisms by which every cell contact in a single sense organ is encoded, and to extend these basic principles to explain how cell shape and cell contacts are specified in other organs, whether it is kidney, gut, heart – or even our own remarkable brains.
Last Update: 8/22/2013