A Competition Mechanism for a Homeotic Neuron Identity Transformation in Caenorhabditis Elegans
By: Patricia Marie Gordon
Publisher: [publisher not identified]
Published: 2015
Place of publication: [New York, N.Y.?]
Language: eng
Description: 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.
Notes: Department: Biochemistry and Molecular Biophysics.

Thesis advisor: Oliver Hobert.

Thesis (Ph.D.)--Columbia University, 2015.