Yale researchers have determined how a key component of the nervous system develops at the embryonic stage. Their work, published June 11 in Cell Reports online, may ultimately offer new approaches to combat major diseases such as diabetes and peripheral artery disease.
A team from Yale Cardiology Research Center collaborated with researchers from Brazil, France, Italy, and Belgium to study sympathetic neurons, cells that play a critical role in regulating the body’s involuntary functions such as circulation, respiration, body temperature, and metabolism. While scientists know that the development of sympathetic neurons relies on the dorsal aorta — the major artery in embryos formed by endothelial and mural cells — the precise mechanism was a mystery.
To explore this question, the team observed zebrafish embryos, which have the unique ability to grow in the absence of blood flow and endothelial cells at different states of development. They found that a certain type of mural cell, known as the vascular mural cell, is the critical piece in the sympathetic neuron puzzle.
Lead authors Stefania Nicoli and Anne Eichmann (cardiology) discovered that vascular mural cells promote differentiation of sympathetic neurons, and revealed the “rules” that govern interactions between endothelial cells, mural cells, and sympathetic neurons. A disruption of these rules may be the root cause of cardiovascular pathologies, including diabetic neuropathy, heart failure, and hypertension, which affect millions of people worldwide.
According to the researchers, this deeper understanding of sympathetic neuron development will enable specific biomedical applications, such as vascular tissue engineering. “By identifying the factors causing mural cells to promote sympathetic neuron differentiation, we may be able to regenerate these neurons,” Eichmann explained.
Source: Ziba Kashef – Yale
Image Credit: The image is credited to Vitor Fortuna
Original Research: Full open access research for “Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons” by Vitor Fortuna, Luc Pardanaud, Isabelle Brunet, Roxana Ola, Emma Ristori, Massimo M. Santoro, Stefania Nicoli, and Anne Eichmann in Cell Reports. Published online June 11 2015 doi: 10.1016/j.celrep.2015.05.028
Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons
•SN precursors close to the DA acquire NA markers (TH and DβH)
•NA differentiation requires vascular remodeling and VMC recruitment
•Inhibition of PDGFR signaling prevents VMC recruitment and NA differentiation
•VMC are sufficient to direct SN development in absence of endothelial cells
The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation.
“Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons” by Vitor Fortuna, Luc Pardanaud, Isabelle Brunet, Roxana Ola, Emma Ristori, Massimo M. Santoro, Stefania Nicoli, and Anne Eichmann in Cell Reports. Published online June 11 2015 doi: 10.1016/j.celrep.2015.05.028