NIH grant: Mechanisms of Left Ventricle Development and Morphogenesis (1R01HL182952-01)

retained text

NIH grant 1R01HL182952-01: Mechanisms of Left Ventricle Development and Morphogenesis
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Neil C Chi. Award: $779600.
Start: 2026-07-10T00:00:00.
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.

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