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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

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Rax regulates hypothalamic tanycyte differentiation and barrier function in mice.

Ana L Miranda-Angulo¹, Mardi S Byerly, Janny Mesa

¹Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287; Institute of Medical Research, Universidad de Antioquia, School of Medicine, Medellín, Colombia 05001000.

The Journal of Comparative Neurology

|August 14, 2013

Summary

The retina and anterior neural fold homeobox transcription factor (Rax) is crucial for hypothalamic tanycyte and ependymal cell development. Rax ensures proper differentiation and organization of these cells, maintaining the cerebrospinal fluid-hypothalamus barrier.

Keywords:

CSF-Brain barrier Rarres2 expression Rax haploinsufficiency ectopic ependymal cells thinning of the third ventricular wall

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Whole-mount Imaging of Mouse Embryo Sensory Axon Projections

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Published on: December 9, 2014

Area of Science:

Neuroscience
Developmental Biology
Cell Biology

Background:

The ventral third ventricle wall comprises tanycytes and ependymal cells, crucial for hypothalamic function.
The transcriptional regulation of tanycyte development and function remains largely unknown.

Purpose of the Study:

To investigate the role of the retina and anterior neural fold homeobox transcription factor (Rax) in hypothalamic tanycyte and ependymal cell differentiation.
To determine if Rax is essential for maintaining the cerebrospinal fluid-hypothalamus barrier.

Main Methods:

Generation and analysis of Rax haploinsufficient mice.
Histological examination of the third ventricular wall.
Assessment of tanycyte and ependymal cell markers.
Evaluation of Evans Blue tracer diffusion.

Main Results:

Rax is selectively expressed in hypothalamic tanycytes.
Rax haploinsufficiency leads to reduced tanycyte and ependymal cell populations and thinning of the third ventricular wall.
Ependymal cells ectopically appear in the α2 tanycytic zone in Rax haploinsufficient mice.
Reduced diffusion of tracer indicates compromised cerebrospinal fluid-hypothalamus barrier function.

Conclusions:

Rax is essential for the normal differentiation and patterning of hypothalamic tanycytes and ependymal cells.
Rax plays a specific role in α2 tanycyte differentiation.
Rax is required for maintaining the integrity of the cerebrospinal fluid-hypothalamus barrier.