How Squid and Octopus Get Their Big Brains

Summary: Neural stem cells of cephalopods act in a similar way to those of vertebrates during nervous system development.

Source: Harvard

Cephalopods — which include octopus, squid, and their cuttlefish cousins — are capable of some truly charismatic behaviors. They can quickly process information to transform shape, color, and even texture, blending in with their surroundings. They can also communicate, show signs of spatial learning, and use tools to solve problems. They’re so smart, they can even get bored.

It’s no secret what makes it possible: Cephalopods have the most complex brains of any invertebrates on the planet. What remains mysterious, however, is the process. Basically, scientists have long wondered how cephalopods get their big brains in the first place?

A Harvard lab that studies the visual system of these soft-bodied creatures — which is where two-thirds of their central processing tissue are focused — believe they’ve come close to figuring it out. The process, they say, looks surprisingly familiar.

Researchers from the FAS Center for Systems Biology describe how they used a new live-imaging technique to watch neurons being created in the embryo in almost real-time. They were then able to track those cells through the development of the nervous system in the retina. What they saw surprised them.

The neural stem cells they tracked behaved eerily similar to the way these cells behave in vertebrates during the development of their nervous system.

It suggests that vertebrates and cephalopods, despite diverging from each other 500 million years ago, not only are using similar mechanisms to make their big brains but that this process and the way the cells act, divide, and are shaped may essentially layout the blueprint required develop this kind of nervous system.

“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,” said Kristen Koenig, a John Harvard Distinguished Fellow and 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.”

The scientists from the Koenig Lab focused on the retina of a squid called Doryteuthis pealeii, more simply known as a type of longfin squid. The squid grow to be about a foot long and are abundant in the northwest Atlantic Ocean. As embryos the look quite adorable with big head and big eyes.

The researchers used similar techniques to those made popular to study model organisms, like fruit flies and zebrafish. They created special tools and used cutting edge microscopes that could take high resolution images every ten minutes for hours on end to see how individual cells behave. The researchers used florescent dyes to mark the cells so they could map them and track them.

This live-imaging technique allowed the team to observe stem cells called neural progenitor cells and how they are organized. The cells form a special kind of structure called a pseudostratified epithelium. Its main feature is the cells are elongated so they can be densely packed.

The researchers also saw the nucleus of these structures move up and down before and after dividing. This movement is important for keeping the tissue organized and growth continuing, they said.

This shows an octopus
It suggests that vertebrates and cephalopods, despite diverging from each other 500 million years ago, not only are using similar mechanisms to make their big brains but that this process and the way the cells act, divide, and are shaped may essentially layout the blueprint required develop this kind of nervous system. Image is in the public domain

This type of structure is universal in how vertebrate species develop their brain and eyes. Historically, it was considered one of the reasons the vertebrate nervous system could grow so large and complex. Scientists have observed examples of this type of neural epithelium in other animals, but the squid tissue they looked at in this instance was unusually similar to vertebrate tissues in its size, organization and the way the nucleus moved.

The research was led by Francesca R. Napoli and Christina M. Daly, research assistants in the Koenig Lab.

Next, the lab plans to look at how different cell types in cephalopod brains emerge. Koenig wants to determine whether they’re expressed at different times, how they decide to become one type of neuron versus another, and whether this action is similar across species.

Koenig is excited about the potential discoveries that lie ahead.

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

About this neuroscience research news

Author: Juan Siliezar
Source: Harvard
Contact: Juan Siliezar – Harvard
Image: The image is in the public domain

Original Research: Closed access.
Cephalopod retinal development shows vertebrate-like mechanisms of neurogenesis” by Kristen Koenig et al. Current Biology


Cephalopod retinal development shows vertebrate-like mechanisms of neurogenesis


  • Retinal progenitor cells in the squid undergo interkinetic nuclear migration
  • Progenitor, post-mitotic, and differentiated cells are transcriptionally defined
  • Notch signaling may regulate both retinal cell cycle and cell fate in the squid


Coleoid cephalopods, including squid, cuttlefish, and octopus, have large and complex nervous systems and high-acuity, camera-type eyes. These traits are comparable only to features that are independently evolved in the vertebrate lineage.

The size of animal nervous systems and the diversity of their constituent cell types is a result of the tight regulation of cellular proliferation and differentiation in development.

Changes in the process of development during evolution that result in a diversity of neural cell types and variable nervous system size are not well understood.

Here, we have pioneered live-imaging techniques and performed functional interrogation to show that the squid Doryteuthis pealeii utilizes mechanisms during retinal neurogenesis that are hallmarks of vertebrate processes.

We find that retinal progenitor cells in the squid undergo nuclear migration until they exit the cell cycle. We identify retinal organization corresponding to progenitor, post-mitotic, and differentiated cells.

Finally, we find that Notch signaling may regulate both retinal cell cycle and cell fate. Given the convergent evolution of elaborate visual systems in cephalopods and vertebrates, these results reveal common mechanisms that underlie the growth of highly proliferative neurogenic primordial.

This work highlights mechanisms that may alter ontogenetic allometry and contribute to the evolution of complexity and growth in animal nervous systems.

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