Multiple functions of Adnp protein in cortical development

What is it about?

Adnp has bifunctional as a transcription factor and a microtubule regulator. Along the neuronal development, the Adnp localization shifts from the nucleus in progenitor cells to the cytoplasm in differentiated neurons. This is regulated by 14-3-3 proteins. Once Adnp is distributed in the cytoplasm, it regulates neurite formation, spine formation, neural connectivity, and neural activity.

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Why is it important?

Activity-dependent neuroprotective protein (ADNP) mutations are among the most common single-gene causes of autism spectrum disorder (ASD) and result in ADNP syndrome, in which ASD is one of the major symptoms. Adnp regulates the expression of over 400 genes and microtubule (MT) activity by binding to MT plus end binding proteins. However,there are limited studies about Adnp functions in cortical development. By using in-utero electroporation technique and ex vivo live imaging, we identified multiple Adnp functions in a variety of cortical developmental steps, including neurite and spine formation and neural connectivity, and calcium influx. We also found the molecular mechanisms underlying the regulation of Adnp distribution along neuronal differentiation. 14-3-3 binds to Adnp and shuttle it from the nucleus to the cytoplasm where Adnp works as a MT regulator.

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