A major challenge in teaching organ development and disease is deconstructing a complex choreography of molecular and cellular changes over time into a linear stepwise process for students. As an entry toward learning developmental concepts, I propose two inexpensive hands-on activities to help facilitate learning of (1) how to identify defects in heart and kidneys and (2) what evolutionarily conserved strategies from organ development can be applied to understand how to repair these defects. The ease of assembling these activities, combined with traffic flow as a metaphor for physiological function of heart and kidneys, provides students the opportunity to explore and discover biological concepts in organ formation and disease.

Organ formation, such as the development of the heart and kidneys, is an important process for physiological function in our bodies. Furthermore, unlocking the complexity of organ development is crucial for insights into how to repair damaged tissue. Understanding how these complex organs are built at the molecular and cellular levels is essential for integrating this topic into the classroom and lab, which inspires discovery-based science inquiry. In order to engage students in the emerging field of lumen formation and luminal interconnection pathologies, or lumopathies, we need a framework for understanding how key signaling modules work together to establish fluid and blood transfer between epithelial and vascular networks (Kao, 2013). Given that the development of these structures is quite complex over space and time, how can we provide useful analogies and hands-on activities to facilitate active learning of these important physiological concepts?

Through my experiences as a Fellow in the translational medicine cohort at the Pacific Science Center, I have developed quick and inexpensive hands-on activities that can be used to facilitate student learning of key principles regarding luminal connections in the kidneys and cardiovascular system. Here, I use dollar-store or recyclable materials to facilitate student–teacher interaction and provide alternative methods that can also facilitate active learning of how a common set of cellular strategies may be used for luminal connection repair. The activities aim to address two questions: (1) How are defects in heart and kidneys identified? (2) What evolutionary strategies are used by different organisms to make connections for fluid or blood flow?

After creating a metaphor comparing stenosis (blood vessel obstruction) and hydronephrosis (water inside kidneys) to traffic jams on highways, I proceed to an important question facing scientists and physicians: How do we identify the defects in traffic flow inside heart and kidneys? The premise of this activity is for students to use colored pipe cleaners to determine which structure contains an obstruction of directional flow (Figure 1). To construct the model for this “Identify the Defect” activity, follow these instructions:

Figure 1.

Assembly of the model for the “Identify the Defect” activity. (A, B) Diagrams illustrating key steps for physiological action in epithelial networks of the kidney. Two different epithelia (blue or green) with preexisting lumens (red), which depict the nephron (blue) and collecting duct (green). Adjacent epithelial networks closely apposed are in “juxtaposition” (A), while luminal connection permits directional flow of fluid (B, red arrows). (C, D) Hands-on activity for identifying defects in kidneys or blood vessel stenosis. A red pipe cleaner represents the connected lumen between two different epithelial and blood-vessel networks (C, red arrow and arrowhead), while the obstruction illustrates occlusion between lumens (D, shortened distance between red arrow and arrowhead).

Figure 1.

Assembly of the model for the “Identify the Defect” activity. (A, B) Diagrams illustrating key steps for physiological action in epithelial networks of the kidney. Two different epithelia (blue or green) with preexisting lumens (red), which depict the nephron (blue) and collecting duct (green). Adjacent epithelial networks closely apposed are in “juxtaposition” (A), while luminal connection permits directional flow of fluid (B, red arrows). (C, D) Hands-on activity for identifying defects in kidneys or blood vessel stenosis. A red pipe cleaner represents the connected lumen between two different epithelial and blood-vessel networks (C, red arrow and arrowhead), while the obstruction illustrates occlusion between lumens (D, shortened distance between red arrow and arrowhead).

  1. Make a small hole in the bottom ends of two plastic cups of different colors, using a drill. The cups should be lightly tinted so that students are able to see the straw during the pipe cleaner test described below. These two tinted cups represent two different tubular structures in the kidney: the collecting duct and nephron. They can also represent venous and arterial vascular networks.

  2. Take a plastic straw with a large enough diameter that a colored pipe cleaner will fit inside it. Make sure that the straw will fit through the holes in the cups. Increase the holes’ diameter with a larger drill bit if necessary.

  3. In one of the straws, create an obstruction by using a pipe cleaner to insert either a cotton ball or a Q-tip (use a fast-bonding glue to hold it in place) into the middle of the straw.

  4. Arrange the two cups prepared in step 1 so that the holes are touching each other, making an hourglass shape.

  5. Insert the obstructed straw through the holes in the cup bottoms so that the ends of the plastic straw reach the open ends (tops) of the cups. Take care that the obstruction is where the two holes meet.

  6. In order to create the model for directed flow, repeat the steps above, but omit step 3, this time inserting an unobstructed straw through the holes in the cup bottoms.

Allow the students to explore which straw is obstructed by letting them use the pipe cleaner to test whether it passes to the other side of the tinted cup (Figure 1C, D). The straw represents the lumen that permits water and salts to pass through tubular segments of the nephron; alternatively, it may also represent the lumen of endothelial cells that form the vascular network, permitting the flow of oxygenated blood throughout the animal. After students have identified the defect, the question in their minds may likely be the following: How do we relieve congested traffic on these microscopic highways that cause these types of kidney and heart defects?

In order to understand how to relieve congested traffic, we need to know how organisms have evolved to generate common sets of strategies for establishing connected tubular networks for traffic flow. The second activity, “Strategies for Repair,” again uses household materials to create a model (Figure 2), in this case to help students explore and discover how a series of different types of strategies are needed to generate a functional connection between two different tubular networks (Figure 3). Here are the instructions for creating the “Strategies for Repair” model:

Figure 2.

Assembly of the model for the “Strategies for Repair” activity. (A) Materials used to make the model. (B) Assembly of circle slits to cover one of the ends of each tube. (C) Construction of the apparatus to symbolize cell rearrangements and cell invasion by tea-bag tab/Q-tip. The tea-bag tab with string (C, dotted line with notched arrow) is connected to the Q-tip (C, arrowhead) and the colored straw (C, arrow). (D) Placement of tea-bag tab/Q-tip at the future site of luminal connection. (E) Another view of the Post-it in relation to the tea-bag tab. (F) Completion of the model.

Figure 2.

Assembly of the model for the “Strategies for Repair” activity. (A) Materials used to make the model. (B) Assembly of circle slits to cover one of the ends of each tube. (C) Construction of the apparatus to symbolize cell rearrangements and cell invasion by tea-bag tab/Q-tip. The tea-bag tab with string (C, dotted line with notched arrow) is connected to the Q-tip (C, arrowhead) and the colored straw (C, arrow). (D) Placement of tea-bag tab/Q-tip at the future site of luminal connection. (E) Another view of the Post-it in relation to the tea-bag tab. (F) Completion of the model.

Figure 3.

“Strategies for Repair”: connecting tubular networks. (A) First, the red pipe cleaner shows lack of connection (A, red arrow). (B) A closer view of the future connection interface, showing the Q-tip blocking the lumen on the left purple flap, while the light blue flap contains the Post-it sticker. (C) The first step requires removal of the Post-it, demonstrating removal of the basement membrane (C, light blue arrow). (D) Next, the tea-bag tag is drawn through into the cyan slit to symbolize cell invasion (D, purple arrow). (E) Finally, a straw lumen is drawn from one side upon alignment of marker ticks; this illustrates cell rearrangements (E, purple arrow). (F) Luminal connection is then verified by showing that the pipe cleaner indeed passes through to the other side (F, red arrow and arrowhead).

Figure 3.

“Strategies for Repair”: connecting tubular networks. (A) First, the red pipe cleaner shows lack of connection (A, red arrow). (B) A closer view of the future connection interface, showing the Q-tip blocking the lumen on the left purple flap, while the light blue flap contains the Post-it sticker. (C) The first step requires removal of the Post-it, demonstrating removal of the basement membrane (C, light blue arrow). (D) Next, the tea-bag tag is drawn through into the cyan slit to symbolize cell invasion (D, purple arrow). (E) Finally, a straw lumen is drawn from one side upon alignment of marker ticks; this illustrates cell rearrangements (E, purple arrow). (F) Luminal connection is then verified by showing that the pipe cleaner indeed passes through to the other side (F, red arrow and arrowhead).

  1. Gather the following materials: two tubes from rolls of toilet paper, a Q-tip, Post-it tape, a tea-bag with string and tab attached, two colors of construction paper, a colored plastic straw, and a colored pipe cleaner (Figure 2A). Have clear tape, scissors, fast-bonding glue, and markers handy.

  2. Use the two colors of construction paper to make two circle flaps to cover one of the open ends of each tube (Figure 2B).

  3. After making marks on each colored circle with a marker, make two orthogonal slits with scissors and then tape a slitted circle to one end of each tube (Figure 2B).

  4. Remove the string (with the tab still attached) from the tea bag, using fingers or scissors (Figure 2C).

  5. Tie the open end of the string to one end of the Q-tip (Figure 2C). Secure it with tape.

  6. Using fast-bonding glue and tape, secure a 3-inch-long straw to the string/Q-tip (Figure 2C). Allow this to dry.

  7. Take the string/Q-tip through one of the open ends of the tube so that the tea-bag tab just comes through the circle slit (Figure 2D).

  8. Finally, place a yellow Post-it (or any colored sticky tab) with the clear end covering the circle slit of the other tube (Figure 2E). Place the circle slits toward each other; this represents the future site of cellular processes prior to luminal connection (Figure 2F).

Once the model for the “Strategies for Repair” activity is constructed, the students are anticipated to make the following sequence of discoveries (Figure 3A–F):

  1. The first step depicts breaking down the milieu of special molecules that form a scaffold called the “basement membrane” (Figure 3C, the removal of a Post-it). Mention to students that removal of the basement membrane allows two tubes to be juxtaposed to one another.

  2. Students will then find a tea-bag tab that can extend and fit into two slits on the other tube (Figure 3D, E). These represent invasive-like behaviors present in the kidney/urogenital system (Chia et al., 2011; Kao et al., 2012) and cell rearrangements in blood vessels (Blum et al., 2008).

  3. Finally, as they draw the straw through the other tube (Figure 3E), they use the pipe cleaner to test whether it goes through to the other side (Figure 3F).

The completion of these steps introduces students to evolutionarily conserved processes that are utilized to permit traffic flow between tubular networks both in kidneys and in blood vasculature development. Furthermore, the “Strategies for Repair” activity can be modified, depending on what cellular processes the teacher wishes to emphasize in his or her lesson plan. These activities will spark students’ curiosity about new ideas on repairing lumopathies.

Acknowledgments

I thank Jennifer Pritchard and Stephanie Fitzwater Arduini for their helpful input and conversations during my fellowship in translational medicine science communications at the Pacific Science Center; Mark Majesky, Lisa Maves, and Xiu Rong Dong for scientific discussions; and an anonymous reviewer for comments. Special thanks to Cindy Kao, Joshua Geiger, and Brie Sullivan for their inspiration during my writing. Robert M. Kao was supported by NIH NIDDK T32007467, “Research Training in Renal Disease.”

References

Blum, Y., Belting, H.-G., Ellertsdottir, E., Herwig, L., Lüders, F. & Affolter, M. (2008). Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo. Developmental Biology, 316, 312–322.
Chia, I., Grote, D., Marcotte, M., Batourina, E., Mendelsohn, C. & Bouchard, M. (2011). Nephric duct insertion is a crucial step in urinary tract maturation that is regulated by a gata3-raldh2-ret molecular network in mice. Development, 138, 2089–2097.
Kao, R.M. (2013). The luminal connection: from animal development to lumopathies. Organogenesis, 9, 111–117.
Kao, R.M., Vasilyev, A., Miyawaki, A., Drummond, I.A. & McMahon, A.P. (2012). Invasion of distal nephron precursors associates with tubular interconnection during nephrogenesis. Journal of the American Society of Nephrology, 23, 1682–1890.