Page 82 - Annual report 2021-22

Annual Report 2021-22 |

Chetana Sachidanandan

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Brain development is a complex but stereotypical process in all organisms. Multiple factors impinge
on the precise regulation of each step of patterning, cell proliferation, migration, differentiation and
functional connectivity. Chetana’s lab uses zebrafish as a model for vertebrate brain development
with a special focus on perturbations that can lead to structural or functional deficits.

Histone acetyl transferases are genes that acetylate histones and regulate gene expression. Mutations
in some of these genes lead to rare mendelian disorders with intellectual disability and cognitive
deficits. Their studies in zebrafish have shown that perturbations in the KAT3 family of histone acetyl
transferases caused not just defects in brain development but also in neural crest migration. Neural
crest defects can explain the pleiotropic effects seen in Rubinstein Taybi syndrome caused by KAT3
mutations.

While mutations in essential genes cause dramatic structural changes in the brain leading to severe
intellectual disability, polymorphisms in other genes lead to more subtle changes in brain
development. These genes are the source of the wide variety of neurodiversity we see among humans.
One such gene is FAM43A, identified in an Indian familial study on dyslexia. Efforts are ongoing to
understand the molecular role of FAM43A in development of neuronal connections and in behavioral
differences using the zebrafish brain as a model.

Yet another influencer of brain development and cognitive changes is the environment the animal
grows up in. It has been established that social interactions play a very important role in slowing down
cognitive decline in the elderly. There is also evidence to suggest that social interactions early in
childhood are crucial for mentally healthy adults. A project using zebrafish as a model to test the effect
of social isolation on behavioral changes in the animal has been initiated with the goal of identifying
the molecular underpinnings of this relationship.