Ultrahigh-Frequency Echocardiography of Autonomic Devoid Phox2B Homozygous Embryos Does Not Reveal a Significant Cardiac Phenotype before Embryo Death

Mokshagundam, Deepa; Kowalski, William J.; Garcia-Pak, Iris; Klaunberg, Brenda A.; Nam, Joseph; Mukouyama, Yoh-suke; Leatherbury, Linda

doi:10.1016/j.ultrasmedbio.2020.11.008

Cited by 2 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disrupting cardiac sympathetic patterning in the embryo leads to postnatal arrhythmia and sudden death ( Ieda et al, 2007 ), while abolishing sympathetic function results in prenatal death due to cardiac failure ( Kobayashi et al, 1995 ; Thomas et al, 1995 ; Zhou et al, 1995 ; Rohrer et al, 1996 ; Baker et al, 2012 ). We have studied the autonomic devoid Phox2b −/− mouse and observed embryo mortality at E13.5-14.5 ( Pattyn et al, 1999 ; Mokshagundam et al, 2021 ). We performed echocardiography to measure cardiac function prior to death, but found no progressive phenotype in Phox2b −/− embryos, suggesting that sudden death due to arrhythmia was the most likely cause.…”

Section: Introductionmentioning

confidence: 99%

Sympathetic Neurons Regulate Cardiomyocyte Maturation in Culture

Kowalski

Garcia-Pak

et al. 2022

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Embryos devoid of autonomic innervation suffer sudden cardiac death. However, whether autonomic neurons have a role in heart development is poorly understood. To investigate if sympathetic neurons impact cardiomyocyte maturation, we co-cultured phenotypically immature cardiomyocytes derived from human induced pluripotent stem cells with mouse sympathetic ganglion neurons. We found that 1) multiple cardiac structure and ion channel genes related to cardiomyocyte maturation were up-regulated when co-cultured with sympathetic neurons; 2) sarcomere organization and connexin-43 gap junctions increased; 3) calcium imaging showed greater transient amplitudes. However, sarcomere spacing, relaxation time, and level of sarcoplasmic reticulum calcium did not show matured phenotypes. We further found that addition of endothelial and epicardial support cells did not enhance maturation to a greater extent beyond sympathetic neurons, while administration of isoproterenol alone was insufficient to induce changes in gene expression. These results demonstrate that sympathetic neurons have a significant and complex role in regulating cardiomyocyte development.

show abstract

Section: Introductionmentioning

confidence: 99%

Sympathetic Neurons Regulate Cardiomyocyte Maturation in Culture

Kowalski

Garcia-Pak

et al. 2022

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…This indicates the critical role of Phox2B in mediating sympathetic development. Indeed, Phox2b homozygous mutant embryos lack autonomic innervation to the heart and die in utero ( Mokshagundam et al, 2021 ; Nam et al, 2013 ). While sympathetic axons innervate various tissue targets, including blood vessels, the mechanisms that regulate tissue-specific innervation are not yet completely understood.…”

Section: Introductionmentioning

confidence: 99%

Vascular smooth muscle cell-derived nerve growth factor regulates sympathetic collateral branching to innervate blood vessels in embryonic skin

Li,

Lipsius,

Burns

et al. 2024

Biology Open

Self Cite

View full text Add to dashboard Cite

Blood vessels serve as intermediate conduits for the extension of sympathetic axons towards target tissues, while also acting as crucial targets for their homeostatic processes encompassing the regulation of temperature, blood pressure, and oxygen availability. How sympathetic axons innervate not only blood vessels but also a wide array of target tissues is not clear. Here we show that in embryonic skin, after the establishment of co-branching between sensory nerves and blood vessels, sympathetic axons invade the skin alongside these sensory nerves and extend their branches towards these blood vessels covered by vascular smooth muscle cells (VSMCs). Our mosaic labeling technique for sympathetic axons shows that collateral branching predominantly mediates the innervation of VSMC-covered blood vessels by sympathetic axons. The expression of nerve growth factor (NGF), previously known to induce collateral axon branching in culture, can be detected in the vascular smooth muscle cell (VSMC)-covered blood vessels, as well as sensory nerves. Indeed, VSMC-specific Ngf knockout leads to a significant decrease of collateral branching of sympathetic axons innervating VSMC-covered blood vessels. These data suggest that VSMC-derived NGF serves as an inductive signal for collateral branching of sympathetic axons innervating blood vessels in the embryonic skin.

show abstract

Ultrahigh-Frequency Echocardiography of Autonomic Devoid Phox2B Homozygous Embryos Does Not Reveal a Significant Cardiac Phenotype before Embryo Death

Cited by 2 publications

References 35 publications

Sympathetic Neurons Regulate Cardiomyocyte Maturation in Culture

Sympathetic Neurons Regulate Cardiomyocyte Maturation in Culture

Vascular smooth muscle cell-derived nerve growth factor regulates sympathetic collateral branching to innervate blood vessels in embryonic skin

Contact Info

Product

Resources

About