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Updated: Aug 23, 2026
Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection
Published on: February 17, 2015
Generating mouse models for studying the function and fate of intrinsic cardiac adrenergic cells
Karl Pfeifer1, Steve P Boe, Qi Rong
1Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. pfeiferk@mail.nih.gov
Abstract:
Embryos lacking the ability to synthesize epinephrine and norepinephrine die (probably due to cardiac failure) without exogenous supplementation while mutant neonates can grow into fertile adults without supplementation. These experiments define a critical period during embryogenesis, when norepinephrine and/or epinephrine are essential for mouse development. The critical period is prior to sympathetic innervation of the heart and prior to synthesis of catecholamines by the adrenal medullae. Recent work indicates that the developing heart is likely to be a major source of catecholamines in the developing mammalian embryo. The spatial pattern of biosynthetic enzymes suggests an association of the intrinsic cardiac adrenergic cells with the developing pacemaker and cardiac conduction cells. To address the functional characteristics and the fate of these cardiac adrenergic cells, we have developed two mouse models that allow us to identify and to characterize the adrenergic cells and their descendants.
Insights
Mouse embryos require epinephrine and norepinephrine for survival during a critical developmental window. This study identifies intrinsic cardiac adrenergic cells as a key source of these essential catecholamines.
Area of Science:
- Developmental Biology
- Molecular Cardiology
- Neuroscience
Background:
- Embryonic development requires precise molecular signaling.
- Catecholamines, like epinephrine and norepinephrine, are crucial signaling molecules.
- The precise role of catecholamines during early embryogenesis is not fully understood.
Purpose of the Study:
- To define the critical period of catecholamine dependency during mouse embryogenesis.
- To investigate the role of intrinsic cardiac adrenergic cells in embryonic development.
- To characterize the function and fate of these cardiac adrenergic cells.
Main Methods:
- Generation of mouse models to identify and track adrenergic cells.
- Analysis of embryonic lethality in mice lacking catecholamine synthesis.
- Histological and molecular characterization of cardiac adrenergic cells.
Main Results:
- Embryos lacking epinephrine and norepinephrine synthesis exhibit embryonic lethality, likely due to cardiac failure.
- This lethality occurs before sympathetic innervation and adrenal medulla catecholamine production.
- Developing hearts are identified as a significant source of embryonic catecholamines.
- Intrinsic cardiac adrenergic cells are spatially associated with developing cardiac pacemaker and conduction cells.
Conclusions:
- Epinephrine and norepinephrine are essential for mouse embryogenesis, particularly for cardiac function.
- Intrinsic cardiac adrenergic cells play a vital role in supplying catecholamines during a critical developmental window.
- Novel mouse models enable detailed study of these crucial cardiac cells and their descendants.
