The people behind the papers – Amber Cook, Taylor Bishop, Hannah Crowe and Andrew Lawton

Left to right: Amber Cook, Hannah Crowe, Taylor Bishop and Andrew Lawton.

Andrew, can you give us your scientific biography and the questions your lab is trying to answer?

AL: As an undergraduate I loved plants and had a chance to work with peach trees at Clemson. But when I arrived at Yale, I saw a time-lapse of cells moving during development and was captured. Scott Holley introduced me to development and quantitative analysis. It was there that I first grew interested in how complex tissue-level morphologies can emerge from cell behaviours. In my postdoc with Alexandra Joyner at Sloan-Kettering I switched to the cerebellum, as it's an exciting problem of morphogenesis. Now, at Mississippi State University we are building from that work and looking at the cellular and tissue-level processes that give rise to the beautiful morphology of the brain.

Amber, Taylor and Hannah, how did you come to work in the lab and what drives your research today?

HC: As a pre-medical undergraduate, I applied to Dr Lawton's summer research position and the rest is history! I was a bit sceptical about lab work, but after two years I have really grown to love ‘thinking like a scientist!’

TB: I learned of Dr Lawton's work in a freshman-year experience course for biology majors and joined his lab two years later. I anticipated learning useful skills, but I never imagined the joy and gratification of working with a team in the unique space of developmental biology.

AC: As a biomedical engineering undergraduate, I grew interested in tissue mechanics and started working with Dr Lawton. When a graduate position became available, I saw it as a perfect opportunity to bring my engineering background to a new field.

What was known about the cellular basis of cerebellar folding before your work?

AL: There is a lot of great work showing that numerous different genetic mutations give rise to phenotypes that include different types of folding disruptions, and there are several predictive models of how brain folding could work. We hoped that by using two ‘wild-type’ strains we could have healthy and ‘normal’ behaving cerebella – just with more or less folding – to investigate some of the tissue-level predictions and to find what cell behaviours may be controlling this more ‘natural’ variation.

Can you give us the key results of the paper in a paragraph?

AC: As predicted, we found that the ‘differential expansion’, the ratio of outer growth to inner growth, correlated with the amount of folding. Surprisingly, the proliferation rate within the outer layer is unchanged between the strains even as they expand to different sizes. The angle of cell division within the outer layer predicts the level of its expansion and may very well be a simple way to adjust the amount of folding.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

HC: When measuring the division angle of the cells I could feel my biology textbooks come to life; everyone learns about chromosomes lining up in the cell to prepare for division, but I got to see it.

And what about the flipside: any moments of frustration or despair?

HC: As an undergraduate I did a lot of measuring, but even more tissue cutting, floating and staining. Rather than yell obscenities at the microtome when things aren't going right, I try to listen to good books or music and think of it as a well-deserved break from schoolwork.

TB: This type of work requires precise handling of the tissue. Getting excellent sections cut and measured was left up to my own two hands which was a magnitude of responsibility I had never known before. The juxtaposition between working quickly and precisely was a battle: frustration and victory.

Were you surprised to find that the cell proliferation rate is less important in determining folding than the cell arrangements within the external granule layer (EGL)?

AL: Perhaps I shouldn't have been, but yes. The proliferation of the EGL is crucial for growing a cerebellum, and for it being folded too. I assumed that increasing the rate of proliferation in the EGL would be a simple way to increase its expansion.

What could be the possible molecular mechanisms underlying the cellular differences that tune the amount of folding?

AL: The EGL is a thick layer of cells that move, proliferate and differentiate. How the cell-division angle is controlled in that context, and how it affects the morphology of the layer are great questions.

Why did you choose to submit this paper to Development?

AC and AL: We like reading Development and thought this work might be a good fit for Development's readership.

Amber, Hannah and Taylor, what is next for you after this paper?

HC and TB: We are starting medical school in fall 2024!

AC: I am working on assays to measure the different directions of tissue tension present during folding development. I am curious about how the different forces within the tissue work with the growth ratios to give rise to the proper morphology of the cerebellum.

Andrew, where will this story take your lab next?

AL: It's been fun to think about the amount of folding, but we'd like to look into the regulation of the pattern of folding too.

Finally, let's move outside the lab – what do you like to do in your spare time?

HC: I bake and sell cakes! It was something my grandmother taught me to do as a child, and I think of her every time I bake.

TB: I enjoy traveling to see all of the views and eat all of the food. I am also perfecting the ultimate chocolate chip cookie recipe!

AC: I love to hike, run, and visit the Noxubee national wildlife refuge.

AL: My five-year-old loves to camp and I need to buy a thicker sleeping bag pad.