The Hatten Lab Projects


Homologs of C. elegans Neuroblast Migration Genes in Mammalian CNS Migrations



To further characterize the mig-13 gene in C. elegans, we are collaborating with the Kenyon Lab at UCSF. Studies are underway to use biochemical approaches to identify the ligand for mig-13 and its downstream signaling pathways. We are also using spinning disc confocal microscopy to image Q neuroblast migration in living worms.

To discover new genes for migration, we are studying homologs of several C. elegans migration. Mammalian genes related to mig-13 include Mmig13, Mlrp3 and Mlrp10, all members of the LRP gene family. Mmig13 is heavily expressed in granule cell precursors as they move across the surface of the embryonic cerebellar anlagen to form the EGL. As EGL cells exit the cell cycle and migrate down along the Bergmann glial fibers, Mmig13 gene expression is down-regulated. Over-expression of Mmig13 by retroviral infection disrupts neuron-glial binding and halts neuronal migration seen in wild type cells suggesting that Mmig13 promotes tangential but not radial cell migrations.

In addition to a role in cerebellar development, Mmig13 is expressed in sensory system domains of the neocortex, including the visual cortex and the somatosensory cortex. During development, Mmig13 is expressed in the pre-plate, where young neurons halt their migrations along glial fibers.

We are presently carrying out detailed studies on the function of Mmig13 in cortical development, using BAC transgenic mice, in vivo electroporation methods, and targeted gene mutations.


In addition to our work with Mmig13, we have recently cloned putative mammalian homologs of the C. elegans gene vab-8, which mediates the posterior migration of several neurons as well as axon pathfinding and axon outgrowth. For the vab-8 homologs, expression is seen in the ventricular zone of the murine neocortex as well as in layers 2,3 of the neocortex. We are carrying out more detailed studies on these genes, generating BAC transgenic mice to further evaluate the dynamics of their expression during brain development.
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