High-Stakes Cellular Process Critical to Small Intestine Development

An intricate cellular dance during embryonic development is critical for normal bowel growth, a new Michigan Medicine study in mice finds.

7:00 AM

Author | Kelly Malcom

High-wire act: Motion of the nucleus of a dividing cell in the developing small intestine.

More than 40 percent of our small intestine develops before we are even born. In adulthood, the organ stretches more than three times the length of our bodies.

But problems with this process in utero can result in a rare but deadly condition known as congenital short bowel syndrome, which can lead to dehydration, malnutrition and weight loss during infancy.

LISTEN UP: Add the new Michigan Medicine News Break to your Alexa-enabled device, or subscribe to our daily audio updates on iTunesGoogle Play and Stitcher.

A new study examining how the developing intestine grows in mice found a surprising sequence of cellular events akin to a death-defying, high-wire circus performance for the organ to reach a proper length. A lack of coordination could have dire consequences.

Sha Wang, Ph.D., and her Michigan Medicine colleagues were able to witness this intricate choreography in real-time in mouse gut cells.

The small intestine, or midgut, starts out as a smooth tube that undergoes rapid growth. Under a microscope, the cells in a thin layer lining the tube — known as epithelial cells — appear to be stacked in layers.

Previously, scientists believed that the tube grew longer via the movement of cells from these apparent stacks into one continuous layer.

"If you think about it, if the midgut lengthened through the convergence of cells, it would sacrifice girth (get thinner). But the tube gets wider," says Wang, a research fellow in the Department of Cell and Developmental Biology at the University of Michigan.

Instead, she and U-M cell biologist Deb Gumucio, Ph.D., and their team were able to show that this elongation is likely powered by rapid cell division. The results are published in Developmental Cell.

A high-stakes process

The team found that during the first phase of midgut development, cells are very tall and thin. The nucleus of each cell moves constantly within the epithelial layer, from the base (or basal) surface to the top (or apical) surface.

MORE FROM THE LAB: Subscribe to our weekly newsletter

In other words, sort of like a trapeze artist climbing up to their starting platform.

"The movement is tied to cell division," says Wang. "Once the nucleus is at the top, the cell will undergo mitosis and split into two new cells."

What happens next is critical. The two new daughter nuclei must make it back to the basal layer in order to re-enter the cell cycle.

For one daughter cell, this step is simple: Its nucleus simply follows a long, thin tether called a basal process back down.

The other cell has a tougher job to do; it must extend an armlike protrusion called a filopodium in the right direction before its nucleus can follow that path back down to the basal surface.

Divide and prosper

Upon closer inspection of the basal process, Wang noticed that this thin tether would often itself divide into two strands — one longer and tethered to the base and one short one that would retract and disappear.

Wang suspects the reabsorbed filament may play a role in dividing the cytoplasm, which makes up most of the body of each new daughter cell.

"The most interesting part is that the cells keep one basal process, which goes to one daughter cell," she says. "The other cell needs to find a connection back to the basal side. Even in the cases where both basal processes are kept, still only one daughter cell keeps them."

Wang hypothesizes that this is done purposefully to give one cell more flexibility for where it lands — but that cell also faces greater risk.

Telling up from down for the nontethered cell, as for a nontethered acrobat, is a matter of life and death.

How cells find their way

The team suspected that there was something serving as a directional cue to help newly formed cells know which way to extend their filopodium.

They settled on a protein known as WNT5A, which is known to help nerve cells grow similar projections called axons. This protein sends out a signal from the tissue, which the new untethered cell will extend toward to make its way back to the basal layer.

SEE ALSO: Study: Vaccine Suppresses Peanut Allergies in Mice

When Wang removed WNT5A, the cells were unable to point themselves in the right direction and died.

And that disconnect can have dire consequences.

Says Wang: "According to our model, even the death of just 10 percent of cells in the midgut can lead to shortened length."

More Articles About: Lab Report Basic Science and Laboratory Research All Research Topics
Health Lab word mark overlaying blue cells
Health Lab

This article is from the Health Lab digital publication.

Media Contact Public Relations

Department of Communication at Michigan Medicine




Get a weekly digest of medical research and innovation, straight to your inbox.

Featured News & Stories microscope cells glioma
Health Lab
Researchers circumvent radiation resistance in subtype of brain tumors
University of Michigan Rogel Cancer Center researchers find ZMYND8 gene plays a critical role in conferring radiation resistance on brain tumors with IDH1 mutation.
Brain wiring diagram prosthetic hand
Health Lab
Simple neural networks outperform the state-of-the-art for controlling robotic prosthetics
Simple neural networks outperform the state-of-the-art for controlling robotic prosthetics
cell slides under microscope
Health Lab
P53 could be key to therapies for salivary gland cancer
Mouse models show that activating a non-mutated form of the gene could lead to developing therapies for this deadly form of cancer. 
Blue green cell microscopic amino
Health Lab
Dietary change starves cancer cells, overcoming treatment resistance
A new study in cells and mice from the University of Michigan Rogel Cancer Center has found that a low-protein diet and a specific reduction in amino acids can improve treatment for colon cancer.
brain stem blue green slice
Health Lab
Monoclonal antibodies preserve stem cells in mouse brains, bring promise for future studies
Using antibodies instead of traditional drugs, stem cells last significantly longer when used in pre-clinical animal models.
cancer cell nucleus virus orange pink
Health Lab
The unique way this virus sneaks into a cell’s nucleus could advance the study of cancer-causing pathogens
Some viruses, like HPV, can cause cancer. Recent investigation into a monkey virus called SV40 may help researchers understand how human oncogenic viruses work, and how to develop more effective treatments.