Sigma Xi Poster Competition
Evaluation of Pancreatic Development in Homozygous Glis3 Mutant Zebrafish
Academic Level at Time of Presentation
Sophomore
Major
Biology/Pre-Medicine
Minor
Chemistry, Psychology
List all Project Mentors & Advisor(s)
Dr. Gary ZeRuth
Presentation Format
Poster Presentation
Abstract/Description
Introduction/Background:
The Krüppellike transcription factor, Gli-Similar 3 (Glis3) has been implicated in several human pathologies including neonatal diabetes, congenital hypothyroidism, and polycystic kidney disease. Numerous genome-wide association studies (GWAS) have additionally identified Glis3 as a risk locus for the development of type 2 diabetes mellitus. Our previous data have suggested possible roles for Glis3 in endocrine pancreas specification but despite its clinical significance, much remains unknown about the role(s) Glis3 plays during development.
Hypothesis/Goal of Study:
In this study, we have characterized developmental expression of glis3 in the zebrafish (Danio rerio) and evaluated the effect of ubiquitous glis3 loss-of-function on pancreas development.
Methods and Results:
Whole-mount in situ hybridization experiments revealed that glis3 was expressed developmentally and was detectable within the pancreas by 72 hpf. A mutant line of zebrafish that lacks functional glis3 expression was generated using CRISPR/Cas9 technology. Homozygous mutant offspring presented with a syndrome including polycystic kidney disease, reduced fertility, and premature mortality by 6 mpf. Although the development of the principal pancreatic islet was largely unaffected by loss of functional glis3, expression of sox9b was significantly reduced fewer homozygous KO larvae had developed secondary islets by 8 dpf. Further, the expression of enteroendocrine hormones including ghrelin, gip, and fgf19 was significantly reduced.
Discussion/Conclusions:
Our results suggest that glis3 is not required for endocrine cell fate specification but may play an important role in the formation of secondary islets and anterior enteroendocrine cells emerging from Notch-responsive progenitors associated with the pancreatic ductal epithelium. A better understanding of role(s) glis3 plays in the maturation of the endocrine pancreas could provide key insights into the pathogenesis of type 2 diabetes.
Spring Scholars Week 2024 Event
Sigma Xi Poster Competition
Evaluation of Pancreatic Development in Homozygous Glis3 Mutant Zebrafish
Introduction/Background:
The Krüppellike transcription factor, Gli-Similar 3 (Glis3) has been implicated in several human pathologies including neonatal diabetes, congenital hypothyroidism, and polycystic kidney disease. Numerous genome-wide association studies (GWAS) have additionally identified Glis3 as a risk locus for the development of type 2 diabetes mellitus. Our previous data have suggested possible roles for Glis3 in endocrine pancreas specification but despite its clinical significance, much remains unknown about the role(s) Glis3 plays during development.
Hypothesis/Goal of Study:
In this study, we have characterized developmental expression of glis3 in the zebrafish (Danio rerio) and evaluated the effect of ubiquitous glis3 loss-of-function on pancreas development.
Methods and Results:
Whole-mount in situ hybridization experiments revealed that glis3 was expressed developmentally and was detectable within the pancreas by 72 hpf. A mutant line of zebrafish that lacks functional glis3 expression was generated using CRISPR/Cas9 technology. Homozygous mutant offspring presented with a syndrome including polycystic kidney disease, reduced fertility, and premature mortality by 6 mpf. Although the development of the principal pancreatic islet was largely unaffected by loss of functional glis3, expression of sox9b was significantly reduced fewer homozygous KO larvae had developed secondary islets by 8 dpf. Further, the expression of enteroendocrine hormones including ghrelin, gip, and fgf19 was significantly reduced.
Discussion/Conclusions:
Our results suggest that glis3 is not required for endocrine cell fate specification but may play an important role in the formation of secondary islets and anterior enteroendocrine cells emerging from Notch-responsive progenitors associated with the pancreatic ductal epithelium. A better understanding of role(s) glis3 plays in the maturation of the endocrine pancreas could provide key insights into the pathogenesis of type 2 diabetes.