Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain development
Version of Record online: 21 DEC 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 232, Issue 2, pages 313–324, February 2005
How to Cite
Seufert, D. W., Prescott, N. L. and El-Hodiri, H. M. (2005), Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain development. Dev. Dyn., 232: 313–324. doi: 10.1002/dvdy.20234
- Issue online: 13 JAN 2005
- Version of Record online: 21 DEC 2004
- Manuscript Accepted: 3 SEP 2004
- Manuscript Revised: 2 SEP 2004
- Manuscript Received: 22 JUN 2004
- Xenopus laevis;
- transcription factor
Mutations in the aristaless-related homeobox (ARX) gene have been found in patients with a variety of X-linked mental retardation syndromes with forebrain abnormalities, including lissencephaly. Arx is expressed in the developing mouse, Xenopus, and zebrafish forebrain. We have used whole-mount in situ hybridization, overexpression, and loss-of-function studies to investigate the involvement of xArx in Xenopus brain development. We verified that xArx is expressed in the prospective diencephalon, as the forebrain is patterned and specified during neural plate stages. Expression spreads into the ventral and medial telencephalon as development proceeds through neural tube and tadpole stages. Overexpression of xArx resulted in morphological abnormalities in forebrain development, including loss of rostral midline structures, syn- or anophthalmia, dorsal displacement of the nasal organ, and ventral neural tube hyperplasia. Additionally, there is a delay in expression of many molecular markers of brain and retinal development. However, expression of some markers, dlx5 and wnt8b, was enhanced in xArx-injected embryos. Loss-of-function experiments indicated that xArx was necessary for normal forebrain development. Expansion of wnt8b expression depended on xArx function as a transcriptional repressor, whereas ectopic expression of dlx5, accompanied by development of ectopic otic structures, depended on function of Arx as a transcriptional activator. These results suggest that Arx acts as a bifunctional transcriptional regulator in brain development. Developmental Dynamics 232:313–324, 2005. © 2004 Wiley-Liss, Inc.