Septins, planar cell polarity, cilia, convergent extension ... Bardet-Biedl and Meckel-Gruber syndromes

Science 29 July 2010
DOI: 10.1126/science.1191184

Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis

Su Kyoung Kim,1,* Asako Shindo,1,* Tae Joo Park,1, Edwin C. Oh,2 Srimoyee Ghosh,1,Ryan S. Gray,1, Richard A. Lewis,3 Colin A. Johnson,4 Tania Attie-Bittach,5 Nicholas Katsanis,2 John B. Wallingford 1,6

The planar cell polarity (PCP) signaling pathway governs collective cell movements during vertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly of cilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease.

1 Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
2 Center for Human Disease Modeling, Departments of Cell Biology and Pediatrics, Duke University, Durham, NC 27710, USA.
3 Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
4 Sections of Ophthalmology and Neurosciences, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, LS9 7TF, UK.
5 Département de Génétique, INSERM U781, Hôpital Necker–Enfants Malades, Université Paris Descartes, Paris, France.
6 Howard Hughes Medical Institute, University of Texas at Austin, Austin, TX 78712, USA.
* These authors contributed equally to this work.
|| To whom correspondence should be addressed. Email:wallingford@mail.utexas.edu

PMID: 20671153

I am quite surprised to see this paper went Science.
It is a paper with nice cell biology images.

But, the molecular mechanism elucidated in the paper is far from satisfaction. Is it because all the developmental biologist doesn't care the molecular mechanism?

I speculate the reason it is a Science paper is because Figure 4E.

• Bardet–Biedl syndrome: wiki, ncbi
• Meckel syndrome: "While not precisely known, it is estimated that the general rate of incidence, according to Bergsma, for Meckel syndrome is 0.02 per 10,000 births. According to another study done six years later, the incidence rate could vary from 0.07 to 0.7 per 10,000 births. ... accounts for 5% of all neural tube defects in Finland."
• Why not perform some kind rescue experiments using those Fritz mutants?
• Fritz with Septins. I don't think the data to link them together are very strong in this paper / not sure about other evidences in the literature.

Any thought?

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