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AREA: Mechanisms underlying epithelial cells? patterning and morphogenesis

Award Number: R15GM101597
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2013
PERIOD OF PERFORMANCE END DATE: 08/31/2022

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AREA: Mechanisms underlying epithelial cells? patterning and morphogenesis - Project Summary: In one of the most common patterning scenarios in animal development, signaling pathways establish domains of gene expression in two-dimensional epithelial sheets. Mutations that are associated with the abnormal development and pathologies of tissues can occur in the source of the signal (trans changes) and/or in the target genes (cis changes). These changes are often deleterious and happen over a relatively short period of time. The same changes are required during speciation. These changes occur over an evolutionary time scale. The Drosophila eggshell is an established model system to study the impact of changes in cell signaling on tissue patterning and morphogenesis. The natural diversity of eggshells among Drosophila species is an emerging area of research. The Yakoby Lab established a new model system, the dorsal ridge, a lumen-like structure on several Drosophila species eggshells. The dorsal ridge was used to study how changes in the spatiotemporal distributions of the TGF-α like ligand Gurken (GRK) change the activation pattern of the epidermal growth factor receptor (EGFR). These changes in trans control the evolution of morphological novelty, which is in contrast to most publications that focus on changes in cis regulation as the driving force behind the evolution of patterning and morphogenesis. This grant aims to study the evolution of several GRK proteins to elucidate the mechanisms of ligand distribution that ultimately control the final shape and size of the dorsal ridge (Aim 1). In addition, it is proposed to study the changes in cis regulation of Broad (BR), a master regulator of respiratory dorsal appendages, on Drosophila eggshells (Aim 2). The pattern of BR is established by an intricate network of transcription factors that are regulated by the EGFR and bone morphogenetic protein (BMP) signaling. Based on the preliminary results, it is proposed that the spatiotemporal difference in the expression patterns of the enhancer controlling the late phase of BR expression is underlying the evolution of the number of dorsal appendages on Drosophila eggshells. Thus, the combination of trans and cis changes underlie the evolution of morphogenesis. The availability of genetic and genome engineering tools together with the sequenced genomes of multiple species, make Drosophila a successful model system to study how changes in signaling and their target genes' network evolved. The Yakoby Lab pioneered the molecular study of dorsal ridge formation as a new model system. Together with their extensive experience in genetic and molecular manipulations of D. melanogaster and other Drosophila species, the Yakoby Lab is in an excellent position to study cis and trans changes that shape the evolution of eggshell morphologies.


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: 2023 ( Subtotal = -$4 )
2023	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	000	2	10/1/2022	COMPETING CONTINUATION	-$4
														Subtotal = -$4

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	000	2	3/2/2022	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	000	2	5/27/2021	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $452,829 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	001	2	9/14/2017	COMPETING CONTINUATION	$452,829
2017	2013	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	000	1	8/30/2017	NEW	$0
														Subtotal = $452,829

Issue Date FY: 2013 ( Subtotal = $353,378 )
2013	2013	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	1	7/19/2013	NEW	$353,378
														Subtotal = $353,378

Grand Total All Awards = $806,203

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AREA: Mechanisms underlying epithelial cells? patterning and morphogenesis

Award Number: R15GM101597

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2013

PERIOD OF PERFORMANCE END DATE: 08/31/2022

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