Obvious Once You See It: #xBio

Apr 28 2014 Published by under EB2014

Sometimes you gets surprise when you peruse meeting abstracts. Like researcher who have gone where they haven't gone before:

Macula densa progenitor cells contribute to nephron formation during kidney development

James Burford, Anne Riquier-Brison, Karie Villanueva, Janos Peti-Peterdi
USC, Los Angeles, CA

Macula Densa

Macula Densa

First, what is the macula densa?

In the cartoon to the right, the glomerulus (filtering unit of the kidney) is shown in yellow with pink blood vessels running in, out, and through it. In blue, between the afferent and efferent arterioles lies a specialized segment of distal nephron. This entire complex is called the juxtaglomerular apparatus. Macula densa cells like next to these blood vessels. These cells look nothing like the rest of the tubule. They almost appear to be upside down, with their metabolic machinery and secretion tools facing the arterioles and glomerular tuft.

The kidney works a lot like those professional organizers with television shows. Instead of picking up trash here and there, removing the bad stuff in a room in a piecemeal fashion, they first empty the room, putting stuff good and bad in the yard or hallway. They then sort through it, putting the keepers back in the room and sending the junk on its way. The glomerulus filters everything out of the blood, and the tubules of the nephron must reabsorb the good stuff. In this case, the trash is usually in the range of 1 to 5 per cent of that which is filtered.

Those tubules have a lot to do.

So let's imagine our TV organizer doing a room in an apartment with a small hall. What if the hallway will not hold all the stuff from the room? Someone has to tell the star that the plan won't work. The hallway has been overwhelmed!

For the kidney, that is the job of the macula densa.

These cells sense the delivery of "stuff" down through the tubule. They can then signal the glomerulus, specifically its arterioles, that they tubule might be getting overwhelmed. This can reduce glomerular filtration, allowing things to proceed at a reasonable pace.

So what did this abstract show?

These investigators produced mice with fluorescent labels localized to their macula densa cells. Unlike people, a full-term mouse pup is still forming nephrons for a few weeks. They turned on these colors on the first day of life for the pups, then looked at their kidneys a few weeks later.

As expected, the macula densa areas lit up. But so did cells in the thick ascending limb of the loop of Henle, downstream from the macula densa.

Why should the macula densa be involved in nephrogenesis?

PCT: proximal convoluted tubule; DCT: distal convoluted tubule

PCT: proximal convoluted tubule; DCT: distal convoluted tubule

You can view a schematic of normal nephron formation here. Tubules arise from nephrogenic blastema and ureteric bud in utero. In the diagram at right, the shaded box indicates the portions that arise from ureteric bud, namely collecting duct (the straight portion) and the connecting tubule, a small area between the distal convoluted tubule (DCT) and the collecting duct.

Of course, nephrons are not this linear in the kidney; there's a reason some parts got named "convoluted!"  The bottom diagram shows, via the dotted arrow, where those glomerular vessels would lie next to the DCT and its macula densa.

Yup, right about where the nephrogenic blastema and ureteric bud parts of the kidney join.MD Location

So it should not surprise anyone that cells in this area might play a rich role in renal development!

Now what about that thick ascending limb (TAL) of the loop of Henle? Even though it's shown below the DCT in our diagrams, the TAL is upstream. What contribution do these cells from the macula densa make in the TAL?

Well, that's the next question, isn't it?

You can catch a platform presentation of this abstract at 9:15 am on Tuesday, April 29, in room 25B of the San Diego Convention Center.

No responses yet

Leave a Reply