“Vigyan Patrika” is a series of author interviews hosted by Bio Patrika. The work described here is done in the lab of Prof. Jonaki Sen in the Department of Biological Sciences & Bioengineering at the Indian Institute of Technology, Kanpur.
Currently, Dr. Kukreja is a Postdoctoral Fellow at the University of Massachusetts Medical School, USA, and Ms. Udaykumar is a PhD student in the Department of Biological Sciences & Bioengineering at the Indian Institute of Technology, Kanpur.
They jointly published a paper titled “Retinoic acid signaling regulates proliferation and lamina formation in the developing chick optic tectum” as joint first authors in Developmental Biology journal (2020).
Author interview
How would you explain your paper’s key results to the non-scientific community?
Our recent study, published in Developmental Biology, provides insight into how the optic tectum in the chick brain develops. The optic tectum is a multilayered structure in the brain that receives visual information from the eye. This information is integrated and transferred to higher visual centers to bring about appropriate responses. Since birds rely heavily on visual cues for survival, this structure is very well developed and is one of the most prominent in the chicken brain.
Several signaling molecules are known to control the development of the optic tectum. Our study showed that one such molecule derived from Vitamin A—retinoic acid (RA)—is crucial for its proper development.
Although RA signaling is known to regulate many aspects of nervous system development, its role in the optic tectum had remained unexplored. We used the chick embryo model, which is ideal because it develops outside the mother’s body, making experimental manipulations easier. Chick embryos are also more cost-effective and accessible than mammalian models like mice.
In previous work, we had observed that the enzyme producing active RA localizes in certain regions of the optic tectum, while the enzyme degrading RA is localized in complementary areas. This suggested that RA signaling isn’t uniform throughout the tectum. We later confirmed the presence of differential RA levels along the anterior-posterior axis.
To study RA’s role, we turned off RA signaling during tectum development. This increased cell proliferation but surprisingly reduced the thickness of the tectal wall. We believe this happens because RA regulates the balance between cell proliferation and differentiation. Without RA, progenitor cells continue dividing without producing enough neurons, leading to thinner tissue.
Additionally, we found that RA also regulates the migration of a subset of neurons. Normally, these neurons migrate in three waves to form distinct layers. Without RA, neurons from the late migratory wave failed to reach their destination, affecting layer formation.
“[…] first time demonstrated that RA signaling is involved in the development of the chick optic tectum and its importance for proper layer formation or lamination of the tectal wall.”
What are the possible consequences of these findings for your research area?
We have, for the first time, demonstrated that RA signaling is essential for the development and lamination of the chick optic tectum. Our study strengthens the known role of RA in maintaining the balance between cell proliferation and differentiation. The precise regulation of cell division and neuron migration at specific time points highlights the multifaceted role of RA within a single tissue.
What was the exciting moment (eureka moment) during your research?
We had two eureka moments. The first was when blocking RA signaling led to the disappearance of certain tectal layers, revealed through anti-MAP2 immunostaining. MAP2 is a protein present in specific tectal layers, so this finding was both unexpected and exciting.
The second moment came when we observed a near two-fold increase in cell numbers per unit area upon RA signaling inhibition. This surprising result showed how significantly RA impacts cell proliferation.
What do you hope to do next?
We now want to explore how RA regulates these processes. Identifying the downstream molecular players will help uncover the mechanisms that control cell proliferation, differentiation, and migration during brain development. This would also improve our broader understanding of brain development.
“[…] Seeing is believing!”
Where do you seek scientific inspiration?
Working with developing chick embryos, we often witness immediate and fascinating changes after experimental manipulation. The real-time nature of these changes during development is awe-inspiring. Our inspiration comes from the phrase: “Seeing is believing!”
How do you intend to help Indian science improve?
India has a high incidence of neurodevelopmental disorders in children aged 2–9. Yet, the causes remain poorly understood. As developmental neurobiologists, our goal is to identify molecular factors underlying these conditions. We hope our research will provide valuable insights and contribute to reducing the occurrence of such disorders in India.
Additionally, our work could help develop new therapeutic and diagnostic tools for improving children’s health worldwide.
Reference
Kukreja S#, Udaykumar N#, Yogesh B, and Sen J. Retinoic acid signaling regulates proliferation and lamina formation in the developing chick optic tectum. Developmental Biology (2020), 467, 95–107. #Equal contribution.
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