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How Squid and Octopuses Grow Their Remarkable Brains

Four Doryteuthis pealeii squid embryos in their egg sac.
Four Doryteuthis pealeii squid embryos in their egg sac. Credit: Kristen Koenig
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A new study finds that cephalopods – a diverse class of mollusks that includes octopuses, squid and cuttlefish – make their brains in a similar way to vertebrates. The study is published in Current Biology.

Extraordinary brainpower

Many cephalopods, despite their unusual appearances, are capable of fascinating and complex behaviors. They can process visual information to rapidly transform in color, shape and even texture. In fact, they are such great communicators and problem solvers that they can even show signs of boredom.


And the cephalopods’ secret weapon? Their amazing brains. Cephalopods have some of the most complex brains of any invertebrate – however, the question of just how they produce these brains has been the subject of much debate among scientists.


Now, Harvard researchers that study the visual systems of these creatures believe they have made a discovery that takes us closer to finally figuring it out, in a process that they say looks remarkably familiar to development in vertebrates.


Scientists from the FAS Center for Systems Biology were able to observe the creation of neurons in a cephalopod embryo using a new live-imaging technique, enabling them to track cells during neural development in the retina.

An eye for detail

While tracking the neural stem cells, the researchers found that they behaved similarly to cells during the development of the vertebrate nervous system. This suggests that, despite vertebrates and cephalopods deviating from one another along the evolutionary tree around 500 million years ago, both groups use similar methods during brain development.


“Our conclusions were surprising because a lot of what we know about nervous system development in vertebrates has long been thought to be special to that lineage,” explained Kristen Koenig, senior author of the study. “By observing the fact that the process is very similar, what it suggested to us is that these two independently evolved very large nervous systems are using the same mechanisms to build them. What that suggests is that those mechanisms — those tools — the animals use during development may be important for building big nervous systems.”


Koenig and colleagues focused their search on the development of retinas in the squid species Doryteuthis pealeii, also known as the longfin squid. These animals can be found in the northwest Atlantic Ocean, growing to around a foot in length. Their embryos are well-known for their adorable appearance, with large heads and big eyes.


The live imaging technique employed by the researchers has also previously been used to study model organisms such as fruit flies and zebrafish. Using cutting-edge microscope technology, high-resolution photographs were taken of the squid embryos every ten minutes over many hours of study, allowing researchers to track the behavior of individual cells with fluorescent dyes.


Their aim was to monitor the organization of a type of stem cell called neural progenitor cells, which together form a distinct tissue structure called a “pseudostratified epithelium”. This appears as a structure of densely packed, elongated cells. In the squid embryos, the researchers observed the nuclei in these cells migrate up and down before and after cell division, an important factor in maintaining organization and healthy growth of the tissue.


This structure is a universal feature of brain and eye development in vertebrates. Previously, it was thought to be a major reason the vertebrate nervous system can grow so large and complex. This type of neural epithelium has been observed in other animals, but the squid tissue examined in this study bore a striking similarity to vertebrate tissues in its size, organization and movement of the nucleus.

Delving deeper into cephalopod brain development

The lab next plans to study the emergence of different cell types within the cephalopod brain, examining whether they appear at different times, what influences the development of one neuron over another and whether these processes are similar in other species.


“One of the big takeaways from this type of work is just how valuable it is to study the diversity of life,” Koenig adds. “By studying this diversity, you can actually really come back to fundamental ideas about even our own development and our own biomedically relevant questions.”


Reference: Napoli FR, Daly CM, Neal S, et al. Cephalopod retinal development shows vertebrate-like mechanisms of neurogenesis. Curr. Biol. 2022. doi: 10.1016/j.cub.2022.10.027


This article is a rework of a press release issued by Harvard University. Material has been edited for length and content.