In the process of building a brain, the use of spatial information to give identity to the various types of neurons that comprise that brain results in a need for neurons to migrate from the position at which they are specified to the position at which they must perform their function. The tangential migration of facial motor neurons in the zebrafish hindbrain provides the ideal system to study the tightly choreographed interaction between a migrating cell and the complex environment through which it is migrating. A forward genetic screen in early pressure (EP) gynogenetic diploids using the tg(Isl1: GFP) line found 17 mutant alleles that have defects in facial motor neuron migration that can be separated into four phenotypic classes. High resolution timelapse imaging reveals that facial motor neurons begin their migration by moving slowly ventrally and posteriorly with their centrosomes and protrusions oriented medially and then, upon contact with the Laminin-containing basement membrane at the r4-r5 boundary, speed up and reorient their centrosomes and protrusions posteriorly. Disruption of the Par complex members aPKCλ, aPKCζ, and Pard6gb results in an ectopic ventral migration of facial motor neurons that, in a phenotype that resembles type II (cobblestone) lissencephaly, results in their escape from the hindbrain. Mosaic analysis reveals that the requirement for aPKC is cell-nonautonomous indicating that it is likely required in the surrounding tissue rather than in facial motor neurons themselves. aPKCλ+ζ double morphant embryos display holes in the ventral Laminin-containing basement membrane through which facial motor neurons have escaped the hindbrain. Ventral facial motor neuron ectopia can be phenocopied by mutation of Lamininal suggesting that it is the defects in Laminin that are the likely cause of ventral mismigration in aPKCλ+ζ double morphants. I conclude that the Laminin-containing ventral basement membrane, properly formed by the action of the Par complex, is both a substrate for migration and a boundary that constrains facial motor neurons to the appropriate migratory path.
|Advisor:||Moens, Cecilia B.|
|School:||University of Washington|
|School Location:||United States -- Washington|
|Source:||DAI-B 71/02, Dissertation Abstracts International|
|Subjects:||Evolution and Development|
|Keywords:||Basement membranes, Facial branchiomotor neurons, Motor neurons, Neuron migration, Polarity|
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