Rax regulates hypothalamic tanycyte differentiation and barrier function in mice
Version of Record online: 15 JAN 2014
Copyright © 2013 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Journal of Comparative Neurology
Volume 522, Issue 4, pages 876–899, March 2014
How to Cite
Miranda-Angulo, A. L., Byerly, M. S., Mesa, J., Wang, H. and Blackshaw, S. (2014), Rax regulates hypothalamic tanycyte differentiation and barrier function in mice. J. Comp. Neurol., 522: 876–899. doi: 10.1002/cne.23451
- Issue online: 15 JAN 2014
- Version of Record online: 15 JAN 2014
- Accepted manuscript online: 12 AUG 2013 06:27AM EST
- Manuscript Accepted: 2 AUG 2013
- Manuscript Revised: 12 JUL 2013
- Manuscript Received: 30 MAY 2013
- National Institutes of Health . Grant Number: R21NS067393
- the National Association for Research in Schizophrenia and Depression (NARSAD)
- the Klingenstein Fund
- W.M. Keck Distinguished Young Scholar in Medical Research (to S.B.)
- Rax haploinsufficiency;
- thinning of the third ventricular wall;
- ectopic ependymal cells;
- Rarres2 expression;
- CSF-Brain barrier
The wall of the ventral third ventricle is composed of two distinct cell populations: tanycytes and ependymal cells. Tanycytes regulate many aspects of hypothalamic physiology, but little is known about the transcriptional network that regulates their development and function. We observed that the retina and anterior neural fold homeobox transcription factor (Rax) is selectively expressed in hypothalamic tanycytes, and showed a complementary pattern of expression to markers of hypothalamic ependymal cells, such as Rarres2 (retinoic acid receptor responder [tazarotene induced] 2). To determine whether Rax controls tanycyte differentiation and function, we generated Rax haploinsufficient mice and examined their cellular and molecular phenotype in adulthood. These mice appeared grossly normal, but careful examination revealed a thinning of the third ventricular wall and reduction of both tanycyte and ependymal markers. These experiments show that Rax is required for hypothalamic tanycyte and ependymal cell differentiation. Rax haploinsufficiency also resulted in the ectopic presence of ependymal cells in the α2 tanycytic zone, where few ependymal cells are normally found, suggesting that Rax is selectively required for α2 tanycyte differentiation. These changes in the ventricular wall were associated with reduced diffusion of Evans Blue tracer from the ventricle to the hypothalamic parenchyma, with no apparent repercussion on the gross anatomical or behavioral phenotype of these mice. In conclusion, we have provided evidence that Rax is required for the normal differentiation and patterning of hypothalamic tanycytes and ependymal cells, as well as for maintenance of the cerebrospinal fluid–hypothalamus barrier. J. Comp. Neurol. 522:876–899, 2014. © 2013 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.