Follow Me! A Tale of Avian Heart Development with Comparisons to Mammal Heart Development

Abstract

Avian embryos have been used for centuries to study development due to the ease of access. Because the embryos are sheltered inside the eggshell, a small window in the shell is ideal for visualizing the embryos and performing different interventions. The window can then be covered, and the embryo returned to the incubator for the desired amount of time, and observed during further development. Up to about 4 days of chicken development (out of 21 days of incubation), when the egg is opened the embryo is on top of the yolk, and its heart is on top of its body. This allows easy imaging of heart formation and heart development using non-invasive techniques, including regular optical microscopy. After day 4, the embryo starts sinking into the yolk, but still imaging technologies, such as ultrasound, can tomographically image the embryo and its heart in vivo. Importantly, because like the human heart the avian heart develops into a four-chambered heart with valves, heart malformations and pathologies that human babies suffer can be replicated in avian embryos, allowing a unique developmental window into human congenital heart disease. Here, we review avian heart formation and provide comparisons to the mammalian heart. J. Cardiovasc. Dev. Dis. 2020, 7, 8 3 of 26 Avian ModelsStudies on avian embryos date back to Aristotle, and even further back, to the Egyptians. Historically, the avian model has played an important role in establishing the foundations in circulation research. Chicken eggs were easy to obtain and could be incubated in ovens [17] to observe different periods of embryo development [18]. William Harvey, for example, used chicken eggs to watch the development of the heart and blood, and was the first to notice the directional flow of blood from the heart into the brain and body during systemic circulation [19]. The existence of capillaries that connected the veins and arteries was confirmed with the aid of a simple microscope by Marcello Malpighi, who also discovered that the heart began to beat before blood started to form [20,21].Avian models have unique characteristics that make them invaluable for embryonic developmental studies and, in particular, heart development research. First of all, like mammals, chickens and quails are amniotes, animals whose embryos develop within an amnion and chorion, and developmental processes are highly conserved among amniotes [22]. Specifically, the development of the avian heart is similar to that of the human heart [23]. The mature avian heart consists of four chambers with valves as well as inflow and outflow connections (veins and arteries, respectively), and despite some differences, it resembles the human heart [24][25][26][27]. Importantly, cardiac defects found in humans can be recapitulated in avian embryos [26][27][28][29]. Second, like humans, avian embryos remain relatively flat from early to late gastrulation stages [30], enabling time-lapse observation of both dorsal and ventral tissues by means of whole-mount ex ovo culture techniques [31,32]. Pioneering w...

Tissue clearing and imaging methods for cardiovascular development

“…Other vertebrate models that are transparent and can be used for in vivo analysis are adult Medaka fish. Also, early avian embryos are transparent and can be used for in ovo imaging of early heart and vasculature development ( Lansford and Rugonyi, 2020 ). However, the number of genetically modified (GFP) lines is limited in avians ( Chapman et al., 2005 ).…”

Heart Development and Regeneration in Non-mammalian Model Organisms

“…Embryonic chicken is a commonly used vertebrate model with the advantage of resembling human heart structure with four-chamber/four-valve configuration and enabling clinically relevant surgical manipulations. It resembles the human heart anatomy more closely than other non-mammalian model organisms (Wittig and Münsterberg, 2016;Lansford and Rugonyi, 2020). Due to the long generation time, genetic methods are not straightforward in chickens.…”

Avian cardiomyocyte architecture and what it reveals about the evolution of the vertebrate heart

“…When comparing animals of similar body size, birds have a nearly twofold larger heart mass than mammals [19][20][21]. This increases stroke volume allowing birds to pump more blood per unit time than mammals [22,23]. Birds also have elevated systolic and diastolic blood pressures compared with similarly sized mammals [20] meaning that stroke work (the product of stroke volume and blood pressure) is higher in birds than mammals [11,21].…”

“…Birds also have elevated systolic and diastolic blood pressures compared with similarly sized mammals [20] meaning that stroke work (the product of stroke volume and blood pressure) is higher in birds than mammals [11,21]. Thus, within the two vertebrate groups demonstrating whole body endothermy, on average the bird heart is capable of equal or greater output than the mammalian heart, a feature which may be necessary to support their elevated body temperature (average bird 41°C, average placental mammal 37°C [22]) and the energetic costs of flight [7,19,24,25].…”