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08-18-2024

Cell nuclei play an unexpected role in organ formation

Organ formation is a symphony of interactions, where each moment is defined by a multitude of exchanges at the microscopic level within our bodies.

Our cells, the fundamental building blocks of life, are in constant communication, orchestrating the formation of embryonic tissues and, ultimately, organs.

Just as vital urban systems like factories and roads ensure the smooth running of a city, organelles within cells perform myriad tasks to enable proper cell function.

Despite being confined within cells, these organelles play a pivotal role in sculpting our organs during embryogenesis.

Understanding the cellular nucleus

The cell nucleus acts as the control center of the cell, storing its genetic material in the form of DNA. This DNA holds the instructions needed for the cell to function, grow, and divide.

Surrounding the nucleus is a double membrane called the nuclear envelope, which protects the DNA and controls what goes in and out. Inside, the DNA is organized into structures called chromosomes, which carry the genes that drive all the cell’s activities.

Beyond managing genetic info, the nucleus also helps produce ribosomes, the cell’s protein factories. Ribosomal RNA (rRNA) is made in a specific area of the nucleus known as the nucleolus.

Once they’re ready, ribosomes exit the nucleus and head into the cytoplasm, where they put together proteins based on the DNA instructions. The nucleus is crucial for keeping genetic information intact and making sure cells work as they should.

Our genes switch on and off based on the signals the nucleus receives. However, the significance of the nucleus extends beyond a simple information processing center.

Its physical characteristics could influence the tissue’s structure as well. Intrigued by this possibility, Professor Otger Campàs and his team from the Cluster of Excellence Physics of Life of TU Dresden embarked on an investigative journey.

How nuclei influence organ formation

Professor Campàs was particularly fascinated with how the physical properties of the nucleus could play a role in tissue formation. 

The initiative was an extension of previous work at the University of California, Santa Barbara.

Armed with a curiosity to discern the role of nuclei in the formation of the vertebrate eye and brain, the researchers arrived at a surprising finding. The stiffness of tissue in the zebrafish retina was contingent on the packing of nuclei.

This revelation was unexpected, given the conventional belief that tissue mechanics depended on cell surface interactions and not internal organelles.

The discovery opens up a new research avenue regarding how cells coordinate embryonic development.

Regulating tissue organization

Past research had unveiled how intercellular forces could liquify tissue to shape embryos. In contrast, it was discovered that the packing of nuclei could solidify the tissue.

Relative sizes of the nucleus and cell had a significant role to play. Experiments and theoretical analysis revealed that tissue stiffness was directly regulated by the nucleus if it occupied most of the cell space.

Moreover, when nuclei packed rigorously, they arranged the cells into nearly crystalline arrays. This novel insight challenged the prevalent beliefs, establishing a previously unseen role for nuclei in regulating tissue organization and mechanics.

Organ formation: The zebrafish model

To further probe the relationship between the size of the cell’s nucleus and organ formation, the team analyzed zebrafish. These creatures offered great insights, thanks to their transparency during embryonic stages and their rapid maturation.

Key observations made in the developing retina and brain of the zebrafish demonstrated that changes in cell and nuclear sizes during the development stage jammed the nuclei into place.

This organization seemed crucial for processing visual cues, with the “crystalline” order of cells appearing as a result of the jamming of nuclei as the eye develops.

Impaired tissue architecture

The research also revealed that brain tissues become nuclear jammed, suggesting a broader role for the nucleus in influencing the architecture of several neural tissues.

The study highlights the possibility of nuclear-level defects causing diseases linked to impaired tissue architecture.

This fresh understanding brings us closer to comprehending how cells construct organs during embryonic development. It pushes the boundaries of our existing knowledge, taking us one step further in our quest to comprehend the intricate marvel of life.

Advancing regenerative medicine

The findings from this research hold significant promise for advancing regenerative medicine.

By understanding the pivotal role that nuclei play in tissue organization and mechanics, scientists may develop strategies to manipulate these processes for therapeutic purposes.

For example, if we can learn to control the packing of nuclei, we could potentially enhance tissue regeneration in damaged organs or even guide the formation of new tissues in lab settings.

This breakthrough could lead to innovative treatments for conditions such as neurodegenerative diseases, where tissue architecture is compromised.

As we delve deeper into the mysteries of cellular organization, the potential applications for improved health outcomes continue to expand, marking an exciting frontier in biomedical research.

The study is published in the journal Nature Materials.

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