ZFIN ID: ZDB-PUB-090521-61
Post-embryonic growth of the zebrafish retina and the anaphase-promoting complex
Wehman, A.M.
Date: 2006
Source: Ph.D. Thesis : 99p (Thesis)
Registered Authors: Wehman, Ann
Keywords: none
MeSH Terms: none
PubMed: none
Stem cells divide to create new cells for growth and regeneration throughout the life of an organism. This requires that some stem cells survive through embryonic stages to function in the adult body. Despite the celebrated therapeutic potential of stem cells, the mechanisms used by the body to regulate stem cell proliferation and quiescence are poorly understood. We performed a forward-genetic screen in zebrafish to discover genes that regulate the division of stem cells specifically in the larval retina. The zebrafish retina is a fantastic system in which to study how stem cells survive embryogenesis and maintain their population at larval and adult stages. The stem cells and their progenitor daughters are found in a stereotyped location at the retinal periphery in a region called the ciliary marginal zone (CMZ) in larvae and adults. In our screen, we discovered mutants where the retina underwent normal development during embryogenesis, but failed to grow normally at larval stages. These mutants fell into two classes, one with a reduced number of cells in the CMZ, and the second with an increased number of cells in the CMZ. We placed these mutants into a hierarchy and propose a model for retinal growth from the CMZ. We went on to identify the genes responsible for the reduced number of cells in the CMZ in two mutants. We discovered that Cdc16 and Cdc26, two subunits of the anaphase-promoting complex/cyclosome (APC/C), are required for the mitotic division of retinal progenitors in the CMZ. Defects in mitotic progression were also observed in tissues beyond the retina and we additionally found that quiescent cells erroneously reenter the cell cycle in the absence of Cdc16 or Cdc26. In addition, we discovered that these proteins are stable and wild-type protein derived from maternally-deposited RNA or protein is still functional at late larval stages in mutant animals. These maternal proteins mask the severity of defects caused by loss of the APC/C.
Ph.D. Thesis, University of California, San Francisco