Evolving Function

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Science  27 Apr 2012:
Vol. 336, Issue 6080, pp. 393
DOI: 10.1126/science.336.6080.393-c

Excessive expansion of a series of glutamine residues in the N terminus of the protein huntingtin (HTT) lies at the root of the neurodegenerative Huntington's disease. Although HTT is evolutionarily conserved, the number of glutamines the gene encodes is not. For example, HTT in the slime mold Dictyostelium discoideum has none of the susceptible glutamines; however, the sea urchin (Strongylocentrotus purpuratus) variant of HTT has two. In mammals, HTT has a larger and more expandable glutamine tract and is expressed in the developing brain, where it is known to regulate neural tube formation. How HTT specifically regulates neurulation, however, is not well understood. Lo Sardo et al. found that mouse embryonic stem cells deficient in HTT expression were also deficient in the intercellular adhesions needed to form neuroepithelial rosettes, hallmarks of neurulation in vitro. The authors tested the ability of N-terminal portions of HTT from other organisms to substitute for the mammalian HTT and found that HTT fragments from the evolutionarily distant Dictyostelium were the least effective. These results suggest a possible connection between the acquisition of a cell adhesion function during the evolution of the HTT protein and the evolution of more complex, centralized neural systems developed by the process of neurulation during embryogenesis.

CREDIT: LO SARDO ET AL. NAT. NEUROSCI. 15, 10.1038/NN.3080 (2012)

Nat. Neurosci. 15, 10.1038/nn.3080 (2012).

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