Pdf

Ofd1, a human disease gene, regulates the length and distal structure of centrioles.

Developmental cell | March 15, 2010 |

Singla, Veena | Romaguera-Ros, Miriam | Garcia-Verdugo, Jose Manuel | Reiter, Jeremy F
Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Abstract

Centrosomes and their component centrioles represent the principal microtubule organizing centers of animal cells. Here, we show that the gene underlyi ... indicate that Ofd1 acts at the distal centriole to build distal appendages, recruit Ift88, and stabilize centriolar microtubules at a defined length.

Centrosomes and their component centrioles represent the principal microtubule organizing centers of animal cells. Here, we show that the gene underlying orofaciodigital syndrome 1, Ofd1, is a component of the distal centriole that controls centriole length. In the absence of Ofd1, distal regions of centrioles, but not procentrioles, elongate abnormally. These long centrioles are structurally similar to normal centrioles but contain destabilized microtubules with abnormal posttranslational modifications. Ofd1 is also important for centriole distal appendage formation and centriolar recruitment of the intraflagellar transport protein Ift88. To model OFD1 syndrome in embryonic stem cells, we replaced the Ofd1 gene with missense alleles from human OFD1 patients. Distinct disease-associated mutations cause different degrees of excessive or decreased centriole elongation, all of which are associated with diminished ciliogenesis. Our results indicate that Ofd1 acts at the distal centriole to build distal appendages, recruit Ift88, and stabilize centriolar microtubules at a defined length.

High Discussion
Low Discussion
Paper
Fig 1
Fig 2
Fig 3
Fig 4
Fig 5
Fig 6
Fig 7

Summary of The Overall Paper

Click to enter summary

Sign up to leave a summary.


Sign up to leave a summary.



Comments
Nihms175669f1
Fig 1. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.
Nihms175669f1
Fig 1. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Fig 1

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms175669f2
Fig 2. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.
Nihms175669f2
Fig 2. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Fig 2

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms175669f3
Fig 3. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.
Nihms175669f3
Fig 3. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Fig 3

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms175669f4
Fig 4. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.
Nihms175669f4
Fig 4. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Fig 4

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms175669f5
Fig 5. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.
Nihms175669f5
Fig 5. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Fig 5

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms175669f6
Fig 6. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.
Nihms175669f6
Fig 6. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Fig 6

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms175669f7
Fig 7. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.
Nihms175669f7
Fig 7. Singla, Romaguera-Ros, et al. "Ofd1, a human disease gene, regulates the length and distal structure of centrioles." Developmental cell 18.3 (2010): 410-24. Web.

Fig 7

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments