Dominican University of California
 

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Presentation or Panel Title

Arrowhead is Required for Intestinal Stem Cell Lineage Maintenance & Proliferative Homeostasis in Drosophila

Location

Guzman Lecture Hall

Start Date

4-15-2016 4:30 PM

End Date

4-15-2016 5:30 PM

Department

Natural Sciences and Mathematics

Student Type

Graduate

Faculty Mentor

Heinrich Jasper, Ph.D. & Maggie Louie, Ph.D.

Presentation Format

Poster Presentation

Abstract/Description

The intestinal epithelium of Drosophila has been used to study the regenerative capacity of intestinal stem cells (ISCs) and the effects it has on endogenous epithelia maintenance mechanisms. ISCs are shown to be responsible for maintaining gut barrier function. Studies have shown that the ability to maintain barrier function is lost with age. Aging promotes a loss in genomic stability which negatively effects tissue maintenance. A recent proliferation study demonstrates LHX4 mRNA levels increase with age, and also increase in malignant colorectal tissue. This study further shows that b-catenin and TCF are required for both benign malignant colorectal growths which are downstream of the Wnt pathway. Similarly, the HOX family gene Awh in Drosophila is orthologous to the LHX family genes found in mammals. Both gene families serve as transcription factors for stress response pathways, regeneration, and development. Conservatively, stem cell expression of Awh suppresses Wnt, and Wnt expression modulates Wnk activity upstream of known cancer promoting pathways. We hypothesized that by studying proliferation as a function age we may unveil genes influencing the activity of known regulatory pathways involved in tissue maintenance. We have shown in an aging genome wide analysis study that the gene Arrowhead (Awh) may influence proliferative homeostasis with age. Here, we validate our GWAS finding by observing the differences in proliferation frequency when Awh expression is reduced in intestinal stem cells; further, we demonstrate the differences between non-mutant and AWH mutant clones by using a known genetic reporter system. Our findings show that reduced endogenous Awh expression in ISCs mimics the phenotypes shown during an age related loss in proliferative homeostasis suggesting a link between age related changes in ISC maintenance and LIM-domain homeobox transcription factors.

Key Words: Intestinal, Stem, Cells, Drosophila, Aging, Arrowhead, Genetics, Conservation, Translational, Biology

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Apr 15th, 4:30 PM Apr 15th, 5:30 PM

Arrowhead is Required for Intestinal Stem Cell Lineage Maintenance & Proliferative Homeostasis in Drosophila

Guzman Lecture Hall

The intestinal epithelium of Drosophila has been used to study the regenerative capacity of intestinal stem cells (ISCs) and the effects it has on endogenous epithelia maintenance mechanisms. ISCs are shown to be responsible for maintaining gut barrier function. Studies have shown that the ability to maintain barrier function is lost with age. Aging promotes a loss in genomic stability which negatively effects tissue maintenance. A recent proliferation study demonstrates LHX4 mRNA levels increase with age, and also increase in malignant colorectal tissue. This study further shows that b-catenin and TCF are required for both benign malignant colorectal growths which are downstream of the Wnt pathway. Similarly, the HOX family gene Awh in Drosophila is orthologous to the LHX family genes found in mammals. Both gene families serve as transcription factors for stress response pathways, regeneration, and development. Conservatively, stem cell expression of Awh suppresses Wnt, and Wnt expression modulates Wnk activity upstream of known cancer promoting pathways. We hypothesized that by studying proliferation as a function age we may unveil genes influencing the activity of known regulatory pathways involved in tissue maintenance. We have shown in an aging genome wide analysis study that the gene Arrowhead (Awh) may influence proliferative homeostasis with age. Here, we validate our GWAS finding by observing the differences in proliferation frequency when Awh expression is reduced in intestinal stem cells; further, we demonstrate the differences between non-mutant and AWH mutant clones by using a known genetic reporter system. Our findings show that reduced endogenous Awh expression in ISCs mimics the phenotypes shown during an age related loss in proliferative homeostasis suggesting a link between age related changes in ISC maintenance and LIM-domain homeobox transcription factors.

Key Words: Intestinal, Stem, Cells, Drosophila, Aging, Arrowhead, Genetics, Conservation, Translational, Biology