Title |
Role of BRCA1 in brain development
|
---|---|
Published in |
Proceedings of the National Academy of Sciences of the United States of America, March 2014
|
DOI | 10.1073/pnas.1400783111 |
Pubmed ID | |
Authors |
Gerald M. Pao, Quan Zhu, Carlos G. Perez-Garcia, Shen-Ju Chou, Hoonkyo Suh, Fred H. Gage, Dennis D. M. O’Leary, Inder M. Verma |
Abstract |
Breast cancer susceptibility gene 1 (BRCA1) is a breast and ovarian cancer tumor suppressor whose loss leads to DNA damage and defective centrosome functions. Despite its tumor suppression functions, BRCA1 is most highly expressed in the embryonic neuroepithelium when the neural progenitors are highly proliferative. To determine its functional significance, we deleted BRCA1 in the developing brain using a neural progenitor-specific driver. The phenotype is characterized by severe agenesis of multiple laminated cerebral structures affecting most notably the neocortex, hippocampus, cerebellum, and olfactory bulbs. Major phenotypes are caused by excess apoptosis, as these could be significantly suppressed by the concomitant deletion of p53. Certain phenotypes attributable to centrosomal and cell polarity functions could not be rescued by p53 deletion. A double KO with the DNA damage sensor kinase ATM was able to rescue BRCA1 loss to a greater extent than p53. Our results suggest distinct apoptotic and centrosomal functions of BRCA1 in neural progenitors, with important implications to understand the sensitivity of the embryonic brain to DNA damage, as well as the developmental regulation of brain size. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 4 | 33% |
Peru | 1 | 8% |
Switzerland | 1 | 8% |
Denmark | 1 | 8% |
Nepal | 1 | 8% |
Unknown | 4 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 50% |
Scientists | 4 | 33% |
Science communicators (journalists, bloggers, editors) | 2 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 3% |
France | 1 | <1% |
Germany | 1 | <1% |
Japan | 1 | <1% |
Canada | 1 | <1% |
Unknown | 113 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 30 | 25% |
Researcher | 26 | 22% |
Student > Master | 12 | 10% |
Student > Bachelor | 9 | 8% |
Professor > Associate Professor | 7 | 6% |
Other | 16 | 13% |
Unknown | 20 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 37 | 31% |
Biochemistry, Genetics and Molecular Biology | 21 | 18% |
Medicine and Dentistry | 13 | 11% |
Neuroscience | 13 | 11% |
Chemistry | 5 | 4% |
Other | 11 | 9% |
Unknown | 20 | 17% |