Cells migrating from the neural crest contribute to the innervation of the venous pole of the heart

Abstract

Cells migrating from the neural crest are known to septate the outflow tract of the developing heart, and to contribute to the formation of the arterial valves, their supporting sinuses, the coronary arteries and cardiac neural ganglia. Neural crest cells have also been suggested to contribute to development of the venous pole of the heart, but the extent and fate of such cells remains unclear. In this study, in the mouse, it is shown that cells from the neural crest contribute to the parasympathetic and, to a lesser extent, the sympathetic innervation of the venous pole of the heart. Nerves within the venous pole of the heart are shown to be of mixed origin, with some being derived from the neural crest, while others have an alternative origin, presumably placodal. The neurons innervating the nodal tissue, which can exert chronotropic effects on cardiac conduction, are shown not to be derived from the neural crest. In particular, no evidence was found to support previous suggestions that cells from the neural crest make a direct contribution to the myocardial atrioventricular conduction axis, although a small subset of these cells do co-localize with the developing left bundle branch. We have therefore confirmed that cells from the neural crest migrate to the venous pole of the heart, and that their major role is in the development of the parasympathetic innervation. In addition, in some embryos, a population of cells derived from the neural crest persist in the leaflets of the atrioventricular valves, but their role in subsequent development remains unknown.

Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates

“…Foxd3 expression is maintained in neural derivatives and downregulated in ectomesenchymal derivatives of NC Vagal NC (from somites one to six) and cardiac NC (from the midotic placode to somite four) are initially overlapping cell populations that innervate the digestive tract and diaphragm, and function in cardiac development by mediating outflow tract septation, contributing VSMCs to the great vessels and generating parasympathetic cardiac ganglia (Allan and Greer, 1997;Hildreth et al, 2008;Hutson and Kirby, 2007;Young and Newgreen, 2001). Foxd3 is differentially required in these NC populations; NCspecific Foxd3-null embryos have no ENS, whereas cardiac outflow tract septation is overtly normal (Teng et al, 2008).…”

How to make a cardiomyocyte

“…The CNCCs arise from the dorsal neural tube and migrate through the pharyngeal arches towards the heart, starting from ∼E10.5. Derivatives of the CNCCs form the parasympathetic innervation of the heart, contribute to the valves, and play a pivotal role in OFT patterning and septation (Hildreth et al, 2008;Hutson and Kirby, 2007;Waldo et al, 2005).…”

Comparative Anatomy and Evolution of the Cardiac Innervation in New World Monkeys (Platyrrhini, E. Geoffroy, 1812)

“…The mammalian and avian ontogenetic developmental studies of the ACNS are detailed in a number of papers (Kirby et al, 1980;Kuratani and Tanaka, 1990;Verberne et al, 1998;Shoba and Tay, 2000;Hildreth et al, 2008Hildreth et al, , 2009). In the chick, the innervation of the outflow tract (arterial porta) by the parasympathetic cardiac branches occurred between stages 28 and 29 of Humburger and Hamilton (HH), whereas the positive HNK1 staining is first observed at the 24th stage and reaches the venous sinus by the 26th stage, and further vagal cardiac branches develop (Kuratani and Tanaka, 1990;Verberne et al, 1998;Hildreth et al, 2009).…”

“…In the chick, the innervation of the outflow tract (arterial porta) by the parasympathetic cardiac branches occurred between stages 28 and 29 of Humburger and Hamilton (HH), whereas the positive HNK1 staining is first observed at the 24th stage and reaches the venous sinus by the 26th stage, and further vagal cardiac branches develop (Kuratani and Tanaka, 1990;Verberne et al, 1998;Hildreth et al, 2009). In the mouse, the parasympathetic vagal nerves are first seen in the venous porta at E10.5 (10.5 days after fertilization, equivalent to HH20 in the chick) and reach the heart by E12.5 (HH24), whereas the innervation of the outflow (arterial porta) occurs slightly later than seen in the chick (Hildreth et al, 2008). The sympathetic cardiac innervation has been shown to occur at later stages than the parasympathetic vagal cardiac innervation in both avian and mammalian species (Kirby et al, 1980;Shoba and Tay, 2000;Hildreth et al, 2009).…”