The chicken embryo model has been used extensively in developmental biology and medical research to study embryonic development and model human diseases. However, like any animal model, the chicken embryo model has some drawbacks and limitations. In this article, we will discuss some of the key disadvantages and limitations of using the chicken embryo for biomedical research.
Difficulties with genetic manipulation
One major disadvantage of the chicken embryo is that it can be difficult to genetically manipulate. Performing targeted genetic modifications like gene knockouts is challenging in birds compared to model organisms like mice or zebrafish.
While methods like CRISPR/Cas9 have enabled genome editing in the chicken embryo, the efficiency is still low. Generating transgenic or knockout chicken lines is time-consuming and costly. The difficulties with genetic manipulation limit the types of research questions that can be easily addressed using the chicken embryo model.
Differences from mammalian embryonic development
There are some key differences between birds and mammals in embryonic development that must be considered when using the chicken embryo as a model system.
For example, chickens rely more heavily on maternal transcripts and proteins deposited in the egg before fertilization. Mammalian embryos undergo more de novo transcription earlier in development. This can limit the chicken embryo’s utility for studying molecular regulation in early embryogenesis.
There are also anatomical differences between avian and mammalian embryos. The extraembryonic membranes and placentation in birds have distinct developmental programs compared to mammals. This could alter how the chick embryo responds to perturbations relative to a mouse or human embryo.
Limitations for modeling human disease
The chick embryo’s evolutionary distance from humans makes it less ideal for modeling certain aspects of human development and disease.
Chickens have a very different anatomy, physiology, lifespan, and genetics compared to humans. Critical processes like placentation, neural tube closure, and cardiogenesis have diverged over ~310 million years of evolution between avian and mammalian lineages.
Subtle differences in the timing, morphology, and molecular signatures of organ development exist. This can limit how well chick embryos recapitulate human embryology and the fidelity of disease models.
Challenges with surgical manipulation
Performing surgical manipulations like tissue transplantations is more challenging in chick embryos compared to mice.
The small size of early chick embryos makes injections and tissue grafting technically difficult. The shell also poses a barrier to accessing the embryo for surgical interventions.
While methods like shell-less culture, ex ovo culture, and embryo imaging have improved the technical limitations, surgical manipulations are still more labor intensive than in mouse embryos.
Limitations for late developmental stages
The utility of the chick embryo model is largely limited to early developmental stages before organogenesis is complete. Maintaining chick embryos ex ovo much beyond day 15 of a 21-day incubation period becomes increasingly difficult.
Studying late developmental events like full maturation of the nervous system, immune system, or organs is therefore challenging. This can restrict experimental questions to early embryogenesis and organogenesis.
Difficulty of antibodies and reagents
There are fewer optimized research tools and reagents for the chick embryo compared to mammalian model systems.
Commercial availability of validated antibodies, reporter constructs, and knockout lines is limited. Generating new tools requires significant optimization for the unique physiological conditions in the avian embryo.
The smaller user base focuses reagent development towards more commonly used model organisms. This practical limitation can hamper pursuing certain research directions.
Lower throughput compared to cell culture
The chicken embryo model has much lower throughput for screening experiments compared to cultured cells. The technical complexity of preparing and manipulating embryos makes it slower and less efficient than simple cell culture.
Chemical screens or morpholino/CRISPR knockdown screens are feasible but may be restricted to hundreds rather than many thousands of conditions. Devices like the chick embryotoxicity screening test have attempted to provide higher throughput in ovo. But in general, the chick embryo’s throughput is far below that of cells.
Restrictions on late-stage drug toxicity testing
Testing developmental toxicity of pharmaceutical compounds requires maintaining the chick embryo until late stages and allowing hatching. However, regulations generally prohibit allowing chick embryos to develop past a midpoint in incubation before an intervention is required.
This significantly restricts the chick embryo’s use for late-stage preclinical toxicity testing in drug development. Teratogenicity testing is primarily limited to the initial two-thirds of development when organogenesis occurs.
Limitations as a replacement for animal models
An important goal in biomedical research is reducing and replacing vertebrate animal use with non-animal alternatives. However, the chick embryo cannot fully replace the utility of other animal models like mice for studying complex physiology or disease in an intact living system.
Mice and other models provide invaluable understanding of how molecular events translate to macroscopic outcomes in a living organism. Simple culture systems cannot replicate these complex feedback mechanisms, regardless of evolutionary proximity to humans.
Thus, while the chick embryo can complement animal research, it exhibits a different set of limitations and does not fully eliminate the need for mammalian models. It is not an exact replacement for other animal systems.
Difficulty of imaging later developmental stages
The chick embryo is an excellent model system for live imaging and visualizing embryonic development. However, most of these imaging capabilities are limited to early stages before the embryo grows and becomes opaque.
As development advances, the embryo becomes larger, more difficult to mount, and visually opaque. Imaging the dynamics of organogenesis, tissue morphogenesis, and cell behaviors in late-stage embryos remains challenging.
Thus, the chick embryo provides a superb visual model for early development, but this benefit is diminished at later stages. Other organisms or tissue culture may be preferable for visualizing certain later developmental events.
Limited commercial infrastructure compared to mice
The ubiquitous use of mouse models has led to extensive commercial infrastructure for generating transgenic strains, isolating embryos, ordering reagents etc. This research infrastructure is far less developed for avian models.
Accessing chick embryos may require developing collaborations with local poultry science departments or commercial egg suppliers. New transgenic lines cannot be ordered from standard animal repositories. Lack ofturn-key commercial services can slow the ease of adopting this model system.
Perceived lack of prestige
Unfortunately, there is sometimes a biased perception that the chick embryo is a dated or simplistic model system. Since the 1920s, the mouse has become the standard model organism in most fields.
Thus, some researchers view the chick embryo as old-fashioned or unsophisticated compared to the genetic tools available in mice. Leading developmental journals may be less enthusiastic regarding purely chick embryo studies.
However, the chick remains one of the most powerful and clinically relevant models for studying embryology, teratology, and morphogenesis. It provides unparalleled visualization of early development. This perceptual bias therefore underestimates the utility of the avian embryo.
Conclusion
The chicken embryo is a tremendously valuable model system that has provided fundamental insights into developmental biology, physiology, and disease for over a century. However, it has some limitations that affect its utility and adoption for addressing different research problems.
Difficulties with genetic manipulation, differences from mammalian development, and limitations to later developmental stages are some key factors that restrict the types of questions that can be readily investigated in the chick embryo.
But the chick embryo retains unique advantages that complement mammalian models and cell culture, rather than serving as an outright replacement. Appreciating both the strengths and limitations of this classic model organism allows researchers to apply it most effectively.
References
Datar, S., & Bhonde, R. (2016). Shell-less chick embryo culture as an alternative in vitro model to investigate glucose-induced malformations in mammalian embryos. Journal of Biosciences, 41(2), 313–321. |
Hirst, C. E., & Marcelle, C. (2015). Avian embryo modeling reveals new insights into the mammalian heart. Circulation Research, 116(5), 817–820. |
Kain, K., Miller, J. W., Jones-Paris, C. R., Thomason, R. T., Lewis, J. D., Bader, D. M., Barnett, J. V., & Zijlstra, A. (2014). The chick embryo as an expanding experimental model for cancer and cardiovascular research. Developmental Dynamics, 243(2), 216–228. |
Makarev, E., & Gorivodsky, M. (2014). Transgenic technology in the chick embryo. Transgenic Research, 23(4), 539–552. |
Sato, Y. (2018). Study of human diseases using chicken embryos: A novel approach for understanding pathogenic mechanisms of human diseases. Organogenesis, 14(3), 86–93. |
Key Takeaways
- Genetic manipulation like gene knockout is more challenging in the chick embryo compared to mammals.
- There are anatomical and developmental differences between birds and mammals that must be considered.
- The utility of the chick for modeling human disease is limited by its evolutionary distance.
- Capabilities for surgical manipulations are restricted in the chick embryo.
- It is difficult to study late developmental stages nearing hatching.
- There are fewer optimized reagents and tools available for the chick embryo.
- Throughput is far lower compared to simple cell culture techniques.
- Regulations prohibit using the chick for pharmaceutical testing past mid-incubation.
- The chick cannot fully replace mammalian models despite its advantages.
- Imaging capabilities are restricted to early development before the embryo becomes opaque.
- Infrastructure for transgenic tools and commercial services is less robust than for mouse models.
- The chick embryo is sometimes undervalued as an outdated or simplistic model.