First published online June 14, 2004
Development 131, 1305e (2004)
© The Company of Biologists Limited
Engrailed: preventing dopaminergic neuron loss
Parkinsons disease (PD) is caused by the loss of dopaminergic
neurons in the substantia nigra, probably through apoptosis. Albéri and
co-workers now report that the engrailed (En) genes are required to prevent
apoptosis of newly-born mesencephalic dopaminergic neurons (see
p. 3229). The
homeobox transcription factors En1 and En2 are expressed in these neurons from
early development to adulthood. In En1/En2-null mice, in
which large areas of the brain are lost, mesencephalic dopaminergic neurons
are generated and become postmitotic but are then lost by birth. The
researchers show that this loss occurs by E14 through apoptosis. In vitro
cell-mixing and RNAi experiments indicate that apoptosis induction occurs
within 24 hours of En downregulation because of a cell-autonomous
requirement for En. The researchers speculate that small changes in
En expression could underlie the slow degeneration of dopaminergic
neurons seen in PD.
Related articles in Development:
- Engrailed genes are cell-autonomously required to prevent apoptosis in mesencephalic dopaminergic neurons
- Lavinia Albéri, Paola Sgadò, and Horst H. Simon
Development 2004 131: 3229-3236.
[Abstract]
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