Missing gene shows the way

For any circuit to function well, the connectivity between its 'switches' has to be correct. In the brain, neurons are like on-off switches, and each neuron has a tree-like arbour of 'input-receiving branches' called dendrites. The extent to which these branches grow and their complexity — how branched they are — are critical in deciding from where a neuron can receive its inputs.

In a work recently published in the journal Science Advances (bit.ly/Lhx2-Mahima), researchers at the Mumbai-based Tata Institute of Fundamental Research (TIFR) have identified a gene that is vital for the stem cells that produce the neurons necessary for the extent and complexity of neuronal dendrites. 

The team that included Mahima Bose and Sreenath Ravindran, doctoral and postdoctoral students respectively of Shubha Tole, Professor of Neuroscience at TIFR, examined neurons in the corpus callosum, a bundle of nerve fibres that carry information between the two halves of the brain.

The Science Advances paper, of which Bose, currently a postdoctoral student at the University of California San Francisco, and Ravindran are first co-authors, studied the gene LHX2, which expresses the transcription factor Lhx2. 

In humans, the loss of LHX2 results in many brain disorders, including the autism spectrum disorder and variable intellectual disability. 

When the LHX2 gene is lost in the stem cells, the scientists found that there is an overexpression of a gene called NEUROG2 that should not be there in mature neurons. "In such a condition, the expression of the NEUROG2 gene is ... 500 times higher than the baseline levels, and this causes the neuron's arbour to shrink," says Tole. 

They also found that the loss of Lhx2 in neurons after the stem cell stage causes shrinkage of the dendrites. The findings can provide insights into circuitry malfunctions that underlie these brain disorders.

"This paper elucidates the stage-specific gene regulatory networks engaged by the Lhx2 transcription factor, which is central to cortical development. The authors show that restriction of NEUROG2 expression by LHX2 is developmental stage-specific and uncover distinct genetic programmes in progenitor (stem) and postmitotic (mature) neurons," says Aurnab Ghose, Professor of Neurobiology at the Indian Institute of Science Education and Research, Pune.