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Publication : Rax regulates hypothalamic tanycyte differentiation and barrier function in mice.

First Author  Miranda-Angulo AL Year  2014
Journal  J Comp Neurol Volume  522
Issue  4 Pages  876-99
PubMed ID  23939786 Mgi Jnum  J:207875
Mgi Id  MGI:5559839 Doi  10.1002/cne.23451
Citation  Miranda-Angulo AL, et al. (2014) Rax regulates hypothalamic tanycyte differentiation and barrier function in mice. J Comp Neurol 522(4):876-99
abstractText  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 alpha2 tanycytic zone, where few ependymal cells are normally found, suggesting that Rax is selectively required for alpha2 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.
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