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Dev Biol. 2017 Oct 1;430(1):156-165. doi: 10.1016/j.ydbio.2017.08.003. Epub 2017 Aug 8.

Three Tctn proteins are functionally conserved in the regulation of neural tube patterning and Gli3 processing but not ciliogenesis and Hedgehog signaling in the mouse.

Author information

1
Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, W404, New York, NY 10065, USA.
2
Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai 201620, China. Electronic address: mengqing@dhu.edu.cn.
3
Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, W404, New York, NY 10065, USA; Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, W404, New York, NY 10065, USA. Electronic address: baw2001@med.cornell.edu.

Abstract

Tctn1, Tctn2, and Tctn3 are membrane proteins that localize at the transition zone of primary cilia. Tctn1 and Tctn2 mutations have been reported in both humans and mice, but Tctn3 mutations have been reported only in humans. It is also not clear whether the three Tctn proteins are functionally conserved with respect to ciliogenesis and Hedgehog (Hh) signaling. In the present study, we report that loss of Tctn3 gene function in mice results in a decrease in ciliogenesis and Hh signaling. Consistent with this, Tctn3 mutant mice exhibit holoprosencephaly and randomized heart looping and lack the floor plate in the neural tube, the phenotypes similar to those of Tctn1 and Tctn2 mutants. We also show that overexpression of Tctn3, but not Tctn1 or Tctn2, can rescue ciliogenesis in Tctn3 mutant cells. Similarly, replacement of Tctn3 with Tctn1 or Tctn2 in the Tctn3 gene locus results in reduced ciliogenesis and Hh signaling, holoprosencephaly, and randomized heart looping. Surprisingly, however, the neural tube patterning and the proteolytic processing of Gli3 (a transcription regulator for Hh signaling) into a repressor, both of which are usually impaired in ciliary gene mutants, are normal. These results suggest that Tctn1, Tctn2, and Tctn3 are functionally divergent with respect to their role in ciliogenesis and Hh signaling but conserved in neural tube patterning and Gli3 processing.

KEYWORDS:

Cilia; Gli2; Gli3; Hedgehog; Tctn1; Tctn2; Tctn3

PMID:
28800946
PMCID:
PMC5831336
DOI:
10.1016/j.ydbio.2017.08.003
[Indexed for MEDLINE]
Free PMC Article

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