This work was conducted in the lab of Prof. Shubha Tole at the Department of Biological Sciences, Tata Institute of Fundamental Research (TIFR), Mumbai.
Currently:
- Dr. Veena Kinare is Assistant Manager, Medical Affairs at Cipla, Mumbai
- Dr. Archana Iyer is a DST INSPIRE Faculty Fellow at TIFR Mumbai
They published a joint first-author paper titled
“An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity”
in Development (2020).
Author interview
How would you explain your paper’s key results to the non-scientific community?
The brain carries out many critical functions, and the hippocampus is a key region responsible for learning and memory. But how does the hippocampus form during development?
We discovered a “molecular toolkit” essential for hippocampal development, involving two proteins — Lhx2 and Ldb1. These proteins bind together like Lego pieces and help bring distant DNA regions closer through DNA looping. This looping influences which genes get turned on or off in developing brain cells.
If either protein is missing, the hippocampus becomes severely underdeveloped. We were able to rescue this defect by inserting a synthetic DNA that creates a fusion protein combining the key parts of Lhx2 and Ldb1. This confirmed that the interaction between these proteins is critical for proper hippocampal formation.
Interestingly, this same interaction was discovered earlier in fruit flies, where it plays a role in wing development. This shows that the mechanism is evolutionarily conserved across species.
“[…] interactions and their downstream effectors can be explored in hippocampal developmental defects.”
What are the possible consequences of these findings for your research area?
Understanding how the hippocampus forms allows us to unravel the complex genetic programs involved in brain development. Our findings could be relevant in understanding developmental brain disorders and might eventually help in developing therapeutic strategies for such conditions.
What was the exciting moment (eureka moment) during your research?
The idea to use a combined Lhx2-Ldb1 protein, inspired by earlier studies in flies, came from a brainstorming session in the lab initiated by a former lab member, Hari Padmanabhan. He made the DNA construct for this “fusion protein.”
We were thrilled to see that this fusion protein rescued hippocampal defects in mutant mice — restoring structural features and marker expression that were otherwise lost. That was our true eureka moment.
What do you hope to do next?
We now aim to explore how the Lhx2-Ldb1 complex operates at a molecular level — especially how it influences chromatin structure and loops distant DNA regions. We’re also interested in identifying other proteins involved in this complex and mapping the chromatin landscape during hippocampal development.
Where do you seek scientific inspiration?
In the words of Richard Feynman, “the pleasure of finding things out” fuels our curiosity. Being part of the research community that asks questions and finds answers that can eventually benefit society is our biggest inspiration.
How do you intend to help Indian science improve?
We actively participate in scientific outreach through school visits and presentations in local languages, particularly in rural areas. By engaging students early on and showing them the real-world impact of research, we hope to inspire the next generation of Indian scientists.
Reference
Kinare V#, Iyer A#, Padmanabhan H, Godbole G, Khan T, Khatri Z, Maheshwari U, Muralidharan B, Tole S.
An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity, Development 147: dev187856 (2020).
# Equal contribution
First authors’ current roles and research interests:
Dr. Veena Kinare
Assistant Manager, Medical Affairs, Cipla, Mumbai
I work in medical affairs, which bridges R&D and commercial teams in pharma. It allows me to apply skills I developed during my PhD—such as literature review, scientific communication, and stakeholder engagement—with doctors, KOLs, and sales/marketing professionals.
Dr. Archana Iyer
DST INSPIRE Faculty Fellow, TIFR Mumbai
I study how brain cells make fate decisions — choosing between becoming neurons or glia. This process, governed by genetic programs and the cellular environment, is crucial for brain function. My work focuses on identifying key molecules regulating this process, especially as it relates to neurodegenerative diseases.
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