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First published online 1 July 2009
doi: 10.1242/dev.033795

Development 136, 2535-2543 (2009)
Published by The Company of Biologists 2009
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Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus

Xi Huang1, Tatiana Ketova1, Jonathan T. Fleming1, Haibin Wang2, Sudhansu K. Dey3, Ying Litingtung1 and Chin Chiang1,*

1 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 4114 MRB III, Nashville, TN 37232, USA.
2 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 10010, China.
3 Division of Reproductive Sciences, Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

* Author for correspondence (e-mail: chin.chiang{at}vanderbilt.edu)

Accepted 18 May 2009

Choroid plexuses (ChPs) are vascularized secretory organs involved in the regulation of brain homeostasis, and function as the blood-cerebrospinal fluid (CSF) barrier. Despite their crucial roles, there is limited understanding of the regulatory mechanism driving ChP development. Sonic hedgehog (Shh), a secreted signal crucial for embryonic development and cancer, is strongly expressed in the differentiated hindbrain ChP epithelium (hChPe). However, we identify a distinct epithelial domain in the hChP that does not express Shh, but displays Shh signaling. We find that this distinct Shh target field that adjoins a germinal zone, the lower rhombic lip (LRL), functions as a progenitor domain by contributing directly to the hChPe. By conditional Shh mutant analysis, we show that Shh signaling regulates hChPe progenitor proliferation and hChPe expansion through late embryonic development, starting around E12.5. Whereas previous studies show that direct contribution to the hChPe by the LRL ceases around E14, our findings reveal a novel tissue-autonomous role for Shh production and signaling in driving the continual growth and expansion of the hindbrain choroid plexus throughout development.

Key words: Shh, Cerebrospinal fluid, Choroid plexus, Epithelium, Gli1


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Development 2009 136: e1502. [Full Text]  





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