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Extracellular regulation of Xenopus development

Award Number: R01HD092990
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2029

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Extracellular regulation of Xenopus development - Summary Cell-cell communication in the early embryo specifies cell fates and orchestrates collective cell movements. One of the main drivers of collective cell behaviors in vertebrates is the core planar cell polarity (PCP) pathway. Genetic studies demonstrated the requirement for vertebrate PCP proteins in many morphogenetic processes including neural tube closure. Our preliminary data revealed the anteroposterior and the mediolateral axes of PCP in the Xenopus neuroectoderm that are marked, respectively, by Vangl2 and Diversin protein clusters. The proposed study will test a hypothesis that the two orthogonal PCP axes are mediated by distinct signaling pathways. This will be achieved using a combination of cell biological, proteomic and live imaging approaches in Xenopus, a powerful experimental model allowing rapid functional analysis in vivo. The medially-enriched PCP clusters will be studied by identifying Diversin- interacting proteins and correlating the dynamics of their assembly and localization with Myosin II-dependent cell behaviors in the neural plate and epidermal ectoderm. The regulation of the anteriorly-enriched PCP clusters and neural tube folding by fibroblast growth factor (FGF) signaling will be investigated and the relevant structural motifs and intracellular pathways will be defined. Wild-type Vangl2 will be compared to mutated Vangl2 constructs that are not sensitive to FGF signaling. The proposed study will reveal the relative contributions of secreted growth factors and actomyosin contractility to morphogenesis in early vertebrate embryos. These experiments will expand the knowledge of morphogenetic mechanisms that are critical for normal development and often disrupted in disease.


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: 2026 ( Subtotal = $475,118 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	000	7	1/21/2026	NON-COMPETING CONTINUATION	$475,118
														Subtotal = $475,118

Issue Date FY: 2025 ( Subtotal = $527,909 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	000	6	12/30/2024	COMPETING CONTINUATION	$527,909
2025	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	001	5	2/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $527,909

Issue Date FY: 2022 ( Subtotal = $416,997 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	000	5	8/8/2022	NON-COMPETING CONTINUATION	$416,997
														Subtotal = $416,997

Issue Date FY: 2021 ( Subtotal = $416,997 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	000	4	8/4/2021	NON-COMPETING CONTINUATION	$416,997
														Subtotal = $416,997

Issue Date FY: 2020 ( Subtotal = $425,508 )
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	000	3	8/12/2020	NON-COMPETING CONTINUATION	$425,508
														Subtotal = $425,508

Issue Date FY: 2019 ( Subtotal = $425,508 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	000	2	8/6/2019	NON-COMPETING CONTINUATION	$425,508
														Subtotal = $425,508

Issue Date FY: 2018 ( Subtotal = $425,508 )
2018	2018	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Child Health and Human Development Extramural Research	000	1	8/28/2018	NEW	$425,508
														Subtotal = $425,508

Grand Total All Awards = $3,113,545

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Extracellular regulation of Xenopus development

Award Number: R01HD092990

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2029

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