Saturday, October 23, 2021 10/23/2021

"Wnt signaling pathway interactions in early anterior-posterior neuroectoderm patterning"

Award Number: R15HD088272
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract The molecular mechanisms by which embryos pattern the early neuroectoderm along the anterior- posterior (AP) body axis and the mechanisms by which Wnt signaling networks govern multiple aspects of development and adult homeostasis are fundamental biological questions. However, much remains to be discovered about each of these questions, especially during the early development of deuterostome embryos where Wnt signaling is essential for anterior-posterior neuroectoderm patterning. We have recently discovered that 3 different, but interconnected, Wnt signaling pathways form a Wnt network that is essential for patterning the neuroectoderm along the anterior-posterior axis in early sea urchin embryos. Comparison of functional and expression studies among multiple deuterostome species (i.e., echinoderms, hemichordates, chordates), including vertebrates, strongly suggests that aspects of this Wnt network are conserved. The long-term goal of the studies in our lab is to systematically characterize the extracellular, intracellular and transcriptional players involved in the Wnt network governing early AP neuroectoderm patterning in the sea urchin. The objective of this R15 is to establish the transcriptional gene regulatory network (GRN) activated downstream of the Wnt network and perform initial functional studies to uncover how extracellular and intracellular Wnt modulators influence the activity of the network. The central hypothesis is that there are key interactions among the signaling pathways at the extracellular, intracellular, and transcriptional level. The rationale is that by first generating the transcriptional GRNs we can better understand how the extracellular and intracellular Wnt network are integrated in the AP neuroectoderm patterning GRN. Aim1 will uncover the transcription factors activated by the Wnt/JNK and Wnt/PKC signaling pathways during AP neuroectoderm patterning using information from differential screens comparing wild type embryos with Wnt/JNK and Wnt/PKC knockdown embryos. Functional gene perturbation studies will be performed to establish the transcriptional GRN scaffold and to define key interactions between the Wnt pathways at the transcriptional level. Aim 2 will use gene perturbation analyses on putative extracellular and intracellular Wnt modulators in order to better characterize the pathway members used in the Wnt/JNK and Wnt/PKC transduction pathways, to identify possible interactions among these modulators between the pathways, and to learn how these modulators affect the emerging GRN created in Aim1. The proposed research is significant because it will be one of the few systematic studies conducted to determine how these Wnt networks influence development in an in vivo model system. It will also provide the baseline for comparative functional studies of the GRN in other deuterostome model species, including vertebrates, thereby filling in large gaps in our knowledge of the evolution of early AP patterning mechanisms.


Issue Date FY	Funding FY	Recipient Name	DUNS Number	City	State	CFDA Number	CFDA Program Title	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = $449,523 )
2021	2021	AUBURN UNIVERSITY	066470972	AUBURN UNIVERSITY	AL	93.865	Child Health and Human Development Extramural Research	000	3	3/5/2021	COMPETING CONTINUATION	$449,523


Issue Date FY: 2020 ( Subtotal = $0 )
2020	2016	AUBURN UNIVERSITY	066470972	AUBURN UNIVERSITY	AL	93.865	Child Health and Human Development Extramural Research	001	2	9/24/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2020	2016	AUBURN UNIVERSITY	066470972	AUBURN UNIVERSITY	AL	93.865	Child Health and Human Development Extramural Research	000	2	9/10/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0


Issue Date FY: 2019 ( Subtotal = $13,366 )
2019	2016	MISSISSIPPI STATE UNIVERSITY	075461814	STATE COLLEGE	MS	93.865	Child Health and Human Development Extramural Research	000	1	12/26/2018	NEW	-$190,797
2019	2016	MISSISSIPPI STATE UNIVERSITY	075461814	STATE COLLEGE	MS	93.865	Child Health and Human Development Extramural Research	002	1	1/25/2019	NEW	$0
2019	2016	AUBURN UNIVERSITY	066470972	AUBURN UNIVERSITY	AL	93.865	Child Health and Human Development Extramural Research	001	2	12/26/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$204,163


Issue Date FY: 2016 ( Subtotal = $422,659 )
2016	2016	MISSISSIPPI STATE UNIVERSITY	075461814	STATE COLLEGE	MS	93.865	Child Health and Human Development Extramural Research	000	1	7/5/2016	NEW	$422,659


Grand Total All Awards = $885,548

Sum of Action Amount is $885,548;

Grand Total = $885,548

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"Wnt signaling pathway interactions in early anterior-posterior neuroectoderm patterning"

Award Number: R15HD088272

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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