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A Competition Mechanism for a Homeotic Neuron Identity Transformation in Caenorhabditis Elegans

Gordon, Patricia Marie

As embryos proceed through development, they must undergo a series of cell fate decisions. At each division, potency is progressively restricted until a terminally differentiated, postmitotic cell is produced. An important part of that cell type determination is repression of alternative fate possibilities. In this thesis, I have explored the mechanisms by which a single transcription factor activates certain cell fates while inhibiting others, using the Caenorhabditis elegans ALM and BDU neurons as a model. ALM neuron identity is regulated by two interacting transcription factors: the POU homeobox gene unc-86 and the LIM homeobox gene mec-3. I investigated fate determination in BDU neurons, the sister cells of ALM. I found that BDU identity is broadly defined by a combination of unc-86 and the Zn finger transcription factor pag-3, while the neuropeptidergic subroutine of BDU is determined by the LIM homeobox gene ceh-14. In addition, I found that reciprocal homeotic transformations occur between ALM and BDU neurons upon loss of either mec-3 or pag-3. In mec-3 mutants, ALM neurons acquire the gene expression profile and morphological characteristics of BDU cells, while in pag-3 mutants, BDU neurons express genes normally found in ALM and change some aspects of their morphology to resemble ALM. While these fate switches appear to be a simple case of cross-repression, the mechanism is in fact more complicated, as pag-3 is expressed not just in BDU but also in ALM. In this thesis, I present evidence that MEC-3 inhibits execution of BDU identity in ALM by physically binding to UNC-86 and sequestering it away from the promoters of BDU genes. This work expands upon the literature examining simultaneous activation of one identity program and repression of alternate programs by introducing a novel mechanism by which a transcription factor competes to direct specific cell fates.

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More About This Work

Academic Units
Biochemistry and Molecular Biophysics
Thesis Advisors
Hobert, Oliver
Degree
Ph.D., Columbia University
Published Here
November 25, 2014