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Mechanisms of Left Ventricle Development and Morphogenesis

Award Number: R01HL182952
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/10/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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Mechanisms of Left Ventricle Development and Morphogenesis - Project Summary How diverse cardiac cell types emerge from developmental heart fields, and how they coordinate to build complex structures such as the left ventricle, which is critical for heart function, remains to be fully defined. To address these questions requires a comprehensive spatiotemporal view of the development of all cardiac cells and the molecular definition of the gene regulatory networks directing their diversification and contribution to distinct cardiac structures. Toward this end, we have recently investigated the developmental origins of cell lineages creating the heart using single cell transcriptomic analyses on Mesp1-cre; Rosa26-tdTomato mouse embryos across key developmental stages of heart development. Computational trajectory analyses of these data predicted at least three developmental heart field progenitor sources including the First and Second Heart Field progenitors as well as an early Hand1-expressing progenitor. In situ and lineage tracing analyses utilizing Hand1-CreERT2 revealed a Hand1-expressing population at the extraembryonic/intraembryonic boundary of the gastrulating embryo that supplies cardiomyocytes residing largely within posterolateral regions of the left ventricle and atrioventricular canal. Notably, the Hand1-CreERT2 lineage created a subset of (rather than all) left ventricle cardiomyocytes, suggesting an unexpected complexity of the development of the left ventricle in which the left ventricle may not develop from a single developmental heart field as previously reported. Thus, we hypothesize that the left ventricle develops from at least two distinct developmental sources which create specific regions (i.e., posterolateral and anteroseptal) of the left ventricle. We propose to: (1) illuminate gene regulatory networks that create and direct distinct developmental heart field progenitors into cardiovascular cell types of the left ventricle/heart, (2) investigate the dynamic spatiotemporal organization of these diverse cardiovascular cell types during left ventricle development and morphogenesis, and (3) functionally examine how developmental heart fields create specific cardiovascular lineages contributing to regions of the developing left ventricle.


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 = $779,600 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cardiovascular Diseases Research	000	1	7/9/2026	NEW	$779,600
														Subtotal = $779,600

Grand Total All Awards = $779,600

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Mechanisms of Left Ventricle Development and Morphogenesis

Award Number: R01HL182952

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/10/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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