What is it about?
We describe a new function for KIF2A in the postnatal brain and provide evidence that KIF2A-related pathologies result from defects in neuronal connectivity and premature neurodegeneration rather than from impaired neurogenesis as commonly assumed. We conditionally deleted KIF2A from progenitors, nascent and mature cortical neurons; and showed that KIF2A is key for maturation and maintenance of neurons. Its deficiency altered MT dynamics, intracellular transport and compromised neuronal connectivity and survival. Our results shed new light on the mechanisms by which KIF2A mutations cause brain diseases.
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Why is it important?
The function of KIF2A during neurogenesis and its relationship with microcephaly have been controversial. Some reports support a role in the proliferation of neural progenitors and others in differentiation of neurons but they all agree that KIF2A deficiency triggers congenital microcephaly. We found that KIF2A is barely detectable in cortical progenitors and its lack has no effect on their proliferation or fate. By contrast, KIF2A is essential in the postnatal brain for microtubule dynamic, neuritogenesis, synaptogenesis, and axonal transport. We conclude that KIF2A is dispensable for embryonic neurogenesis but crucial for neuronal maturation, connectivity, and survival.
Perspectives
This article sheds new light on the mechanisms of action of KIF2A and links neurodevelopment to neurodegeneration. It will help colleagues rethink the way they interpret and handle KIF2A-related pathologies
Prof Fadel Tissir
Hamad Bin Khalifa University
Read the Original
This page is a summary of: KIF2A deficiency causes early-onset neurodegeneration, Proceedings of the National Academy of Sciences, November 2022, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2209714119.
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