Lhx genes are a sub-family of Hox genes that play important roles in animal development.
In Caenorhabditis elegans there are seven Lhx genes, including the founding
family member lin-11. The lin-11 gene is necessary for the specification of neuronal
and reproductive tissues. My thesis work has involved understanding the mechanism of
lin-11 regulation and its function in these tissues. To this end, I addressed two distinct
but complementary questions, one of which focused on how transcriptional regulation of
lin-11 occurs and the second on the role of LIN-11 protein domains/regions.
My work on the transcriptional regulation has uncovered important roles of two of the
largest lin-11 introns, intron 3 and intron 7. These introns promote lin-11 expression
in non-overlapping sets of amphid neurons. Based on gene expression patterns and
behavioural assays, intron 3 is capable of restoring lin-11 function in lin-11(n389 ) null
mutant allele. Comparison of intron 3-driven reporter expression in the neuronal cell
types between C. elegans and C. briggsae has revealed cis and trans evolutionary changes
in lin-11 regulation between the two species. Functional dissection of the introns in C.
elegans has led to the identification of three distinct non-overlapping enhancers, each
specific for a single amphid neuron, i.e., RIC, AIZ, and AVG. I have also identified
four transcription factors, SKN-1, CEH-6, CRH-1, and CES-1, that act through these
enhancers to regulate neuronal expression of lin-11.
Furthermore, I have characterized the function of the LIM domains and a proline-rich
(PRR) C-terminus region of LIN-11 in the specification of neuronal and reproductive
tissues. My work shows that while the LIM domains are required for LIN-11 function
in these tissues, the PRR region is dispensable. I have also examined the functional
conservation of lin-11 domains using two other Lhx genes, Drosophila melanogaster
(dLim1) and Mus musculus (Lhx1 ), and found that both of these genes were able to
rescue lin-11 defects. Together, my work has significantly advanced our understanding
of transcriptional regulation of lin-11, the importance of LIM domains in tissue formation,
and functional conservation of Lhx genes across phyla. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21959 |
| Date | January 2017 |
| Creators | Amon, Siavash |
| Contributors | Gupta, Bhagwati, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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