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Evaluation of endocrine pancreas development, beta cell mass expansion, and regeneration in glis3 mutant zebrafish

Award Number: R15DK122547
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/07/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Evaluation of endocrine pancreas development, beta cell mass expansion, and regeneration in glis3 mutant zebrafish - Project Summary The endocrine pancreas is responsible for the production of several hormones, including insulin, important in the regulation of carbohydrate metabolism and glucose homeostasis. Both the development of the endocrine pancreas and its proper function within the context of the mature organ rely on networks of transcription factors that are not yet well understood. Among these, the Krüppel-like protein, Gli-similar 3 (Glis3) has been found to be important in the development of insulin-producing β cells and is essential for insulin transcription in adults. Currently, little is known about the specific roles Glis3 plays in pancreatic cell fate specification or its involvement in the postnatal expansion of β cell mass. In this proposal, experiments are described intended to characterize pancreatic development and function in the glis3sa17645 mutant zebrafish line. Zebrafish homozygous for the glis3sa17645 allele (glis3-/-) ubiquitously lack glis3 expression. In Specific Aim 1, we will characterize pancreatic development in glis3 knockout fish to determine whether glis3 is required for the formation of endocrine progenitor cells or their subsequent specification to islet fates. Emphasis will be placed on identifying the mechanisms that regulate islet maturation and mass expansion. The experiments described in Specific Aim 2 are designed to examine the role of glis3 in the expansion of β cell mass in adults responding to nutrient excess. Finally, in Specific Aim 3, β cell regeneration will be studied in glis3 mutant zebrafish following chemical ablation. The research described in this proposal will be conducted at a regional comprehensive university that serves a predominately rural, economically underdeveloped community for whom access to scientific research is traditionally restricted. The research will be completed with extensive support from undergraduate researchers who will gain the opportunity to co-author manuscripts and present findings at local, state, and national meetings. Broadly, the completion of the studies outlined in this proposal will increase our understanding of how Glis3 specifies endocrine fates in the pancreas and may help shed light on how Glis3 mutations lead to diseases in humans including diabetes mellitus. Furthermore, a greater understanding of the mechanisms that regulate pancreatic development is likely to be achieved including a more thorough knowledge of the transcription factor networks that regulate β cell mass expansion and regeneration in zebrafish. Ultimately, completion of the research described may lead to the establishment of a complementary zebrafish model for the study of diabetes or other Glis3-related diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$108,321 )
2025	2020	MURRAY STATE UNIVERSITY	200 SPARKS HALL	MURRAY	KY	42071	CALLOWAY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/18/2024	NEW	-$108,321
														Subtotal = -$108,321

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	MURRAY STATE UNIVERSITY	200 SPARKS HALL	MURRAY	KY	42071	CALLOWAY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/14/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $286,948 )
2020	2020	MURRAY STATE UNIVERSITY	102 CURRIS CENTER	MURRAY	KY	42071	CALLOWAY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/6/2020	NEW	$286,948
														Subtotal = $286,948

Grand Total All Awards = $178,627

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Evaluation of endocrine pancreas development, beta cell mass expansion, and regeneration in glis3 mutant zebrafish

Award Number: R15DK122547

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/07/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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