. 2016 Nov 23;92(4):813-828.

doi: 10.1016/j.neuron.2016.09.056. Epub 2016 Oct 27.

Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate

Affiliations

¹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA.
² Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
³ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
⁴ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
⁵ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Pediatric Neurology Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁶ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
⁷ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
⁸ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
⁹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA. Electronic address: timothy.yu@childrens.harvard.edu.
¹⁰ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: byoung-il.bae@yale.edu.
¹¹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: christopher.walsh@childrens.harvard.edu.

PMID: 27974163
PMCID: PMC5199216
DOI: 10.1016/j.neuron.2016.09.056

Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate

Divya Jayaraman et al. Neuron. 2016.

. 2016 Nov 23;92(4):813-828.

doi: 10.1016/j.neuron.2016.09.056. Epub 2016 Oct 27.

Authors

Affiliations

¹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA.
² Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
³ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
⁴ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
⁵ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Pediatric Neurology Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁶ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
⁷ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
⁸ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
⁹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA. Electronic address: timothy.yu@childrens.harvard.edu.
¹⁰ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: byoung-il.bae@yale.edu.
¹¹ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: christopher.walsh@childrens.harvard.edu.

PMID: 27974163
PMCID: PMC5199216
DOI: 10.1016/j.neuron.2016.09.056

Abstract

Mutations in several genes encoding centrosomal proteins dramatically decrease the size of the human brain. We show that Aspm (abnormal spindle-like, microcephaly-associated) and Wdr62 (WD repeat-containing protein 62) interact genetically to control brain size, with mice lacking Wdr62, Aspm, or both showing gene dose-related centriole duplication defects that parallel the severity of the microcephaly and increased ectopic basal progenitors, suggesting premature delamination from the ventricular zone. Wdr62 and Aspm localize to the proximal end of the mother centriole and interact physically, with Wdr62 required for Aspm localization, and both proteins, as well as microcephaly protein Cep63, required to localize CENPJ/CPAP/Sas-4, a final common target. Unexpectedly, Aspm and Wdr62 are required for normal apical complex localization and apical epithelial structure, providing a plausible unifying mechanism for the premature delamination and precocious differentiation of progenitors. Together, our results reveal links among centrioles, apical proteins, and cell fate, and illuminate how alterations in these interactions can dynamically regulate brain size.

Keywords: Aspm; Wdr62; apical complex; maternal centriole.

PubMed Disclaimer

Figures

**Figure 1. *Wdr62* and *Aspm* interact genetically to control brain size in mice**
(A) Table of expected genotypic classes, Mendelian ratios, and predicted vs. observed numbers of progeny resulting from crossing *Wdr62 +/−; Aspm +/−* × *Wdr62 +/−; Aspm +/−* mice (trans het × trans het). Chi square test, p < 0.0001. (B) Brain weights measured at P30 show a declining trend, with *Wdr62 +/−; Aspm −/−* and *Wdr62* −/− mice showing a significant reduction in brain weight compared to WT and het controls, as well as *Aspm −/−* mice. Error bars indicate mean ± SEM. “ns” = not significant. * = p < 0.05. (C) P30 coronal brain sections of various genotypes (from left to right: WT, *Wdr62 +/−; Aspm +/−, Aspm −/−, Wdr62 +/−; Aspm −/−* and *Wdr62 −/−*) stained for Cux1 (to label upper layers) and NeuN (to label all neurons) show a severe reduction in overall brain size in the *Wdr62 +/−; Aspm −/−* and the *Wdr62 −/−*. Scale bar = 500 µm. (D) P10 coronal brain sections (from left to right: WT, *Aspm +/−, Wdr62 +/−, Wdr62 +/−; Aspm +/−, Aspm −/−, Wdr62 +/−; Aspm −/−* and *Wdr62 −/−*) showing primary somatosensory cortex (barrel region) stained for Cux1 and Ctip2 to label upper layers (II–IV) and lower layers (V–VI), respectively. Overall cortical thickness and upper layer thickness are severely reduced in the *Wdr62 −/−* brain and the *Wdr62 +/−; Aspm −/−* brain, with a mild reduction in thickness of the upper layers in the *Aspm −/−* cortex. Scale bar = 100 µm. (E–G) * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 and “ns” = not significant. *Wdr62 +/−* and *Aspm +/−* are not significantly different from WT (not shown). Error bars indicate mean ± SEM. (E) Quantification of overall cortical thickness. (F) Quantification of thickness of upper layers. *Wdr62 +/−* and *Aspm +/−* are not significantly different from WT in upper layer thickness (not shown). (G) Quantification of ratio of Cux1+ cells to Ctip2+ cells. See also Supplemental Figure S1.

**Figure 2. Loss of *Wdr62* and *Aspm* results in apical to basal progenitor fate switch with expansion beyond the germinal zones in developing neocortex**
(A) Loss of *Wdr62* and *Aspm* results in expansion of the Tbr2+ basal progenitor pool at E14.5. Left to right: WT, *Wdr62 +/−; Aspm +/−, Aspm −/−, Wdr62 +/−; Aspm −/−* and *Wdr62 −/−* cortex stained for Sox2 (blue), Tbr2 (red) and Tbr1 (green) to label apical progenitors (APs) in the ventricular zone (VZ), basal progenitors (BPs) in the subventricular zone (SVZ) and neurons in layer VI of the cortical plate (CP), respectively. Scale bar = 25 µm. (B) Quantification of ratio of Tbr2+ / Sox2+ cells in (A). (C) Relative decrease in Pax6+ APs in *Wdr62 −/−* cortex at E14.5. Left to right: WT, *Aspm −/−, Wdr62 +/−; Aspm −/−* and *Wdr62 −/−* cortex stained for Pax6 (red) and Ki67 (blue) reveals an increase in the proportion of Ki67+ cycling cells that are Pax6− in the mutants, esp. *Wdr62 −/−*. Scale bar = 50 µm. (D) Quantification of Ki67+Pax6− cells per 100 µm of ventricular surface in (C). (E) Ectopic Tbr2+ basal progenitors outside the SVZ in *Wdr62 −/−* cortex at E14. Left to right: WT, *Wdr62 +/−, Aspm −/−, Wdr62 +/−; Aspm −/−* and *Wdr62 −/−* cortex stained for Ki67 (blue) and Tbr2 (red) to label proliferating cells and basal progenitors, respectively. The thickness of the region containing Ki67+ proliferating cells is marked by the bottom and middle hash lines, while the thickness of the entire cortex is marked by the bottom and top hash lines. Scale bar = 50 µm. (F) Quantification of thickness of Ki67+ cells / overall cortical thickness shows that Ki67+ cells are expanded beyond the germinal zones (VZ/SVZ) in the mutants relative to the controls, suggesting that the neural progenitors are delocalized from the VZ/SVZ. (G) Minimal apoptosis in single and double mutant cortex at E14. Left to right: *Wdr62 +/−* (negative control), *Wdr62 −/−, Wdr62 +/−; Aspm −/−* and *Katnb1* homozygous gene-trap (positive control) mouse brain sections, stained for activated caspase-3 (red) and counterstained with DAPI. Scale bar = 25 µm. (H) 3D en face analysis of spindle orientation shows no significant difference in mitotic spindle orientation of neural progenitors between WT, *Wdr62 +/−; Aspm −/−* and *Wdr62 −/−* embryos. Shown are box and whisker plots quantifying the spindle orientation of VZ progenitors in anaphase at E14.5 in WT (n = 60 cells, 4 animals), *Wdr62 +/−; Aspm −/−* (n = 40 cells, 3 animals) and *Wdr62 −/−* (n = 49 cells, 3 animals). Box boundaries extend from 25^th to 75^th percentiles; the line in the middle and the cross represent the median and mean, respectively. The whiskers denote the range of values from smallest to largest. See also Supplemental Figure S2.

**Figure 3. *Wdr62* and *Aspm* genetically interact to control centriole duplication**
(A) Mouse embryonic fibroblasts (MEFs) stained with Centrin (green) and Cyclin A (red) to mark centrioles and S-phase/G2 cells, respectively, showing that loss of *Wdr62, Aspm* or both leads to underduplication of centrioles. Left to right: Wild-type (WT), *Wdr62 −/−, Aspm −/−, Wdr62 +/−, Aspm +/−, Wdr62 +/−; Aspm −/−*. Insets (in grayscale) show Centrin staining at higher magnification. Scale bar = 10 µm. (B) EM of representative WT (left), *Aspm −/−* (middle) and *Wdr62 −/−* (right) MEFs, with white dotted ovals or circles outlining the individual centrioles. Pairs of centrioles are seen in WT MEFs, while only one unpaired centriole is visible in *Aspm −/−* and *Wdr62 −/−* MEFs. Scale bar = 100 nm. (C) Serial EM confirms centriole duplication defect in *Wdr62* +/−*; Aspm* −/− mouse embryonic fibroblasts (MEFs). Left: White rectangles and circles outline the pair of centrioles in serial sections of a representative WT cell. Right: Only one centriole (outlined in white) is visible through several serial sections of a representative *Wdr62 +/−; Aspm −/−* cell. Scale bar = 20 nm. (D) Quantification of centriole number in S-phase cells of various genotypes indicates that the severity of the centriole duplication defect is proportional to the severity of the microcephaly phenotype. N = 200–300 cells per genotype. Fisher’s exact test, “ns” = not significant, * = p < 0.05 and **** = p < 0.0001 (compared to WT unless otherwise indicated). See also Supplemental Figure S3.

**Figure 4. WDR62 recruits ASPM to form a physical complex at the mother centriole**
(A–B) WDR62 and ASPM are proximal centriole proteins required for centriole duplication in human cells. Using two distinct siRNAs against human *WDR62 (WDR62 #1 and WDR62 #2)* and *ASPM* (*ASPM #1* and *ASPM #2*), the centrosomal signal can be abolished in metaphase and S-phase transfected cells. The majority of WDR62- and ASPM-depleted cells had two or three centrioles. Insets: c = Centrin; w = WDR62 and a = ASPM. (A) WDR62 and ASPM localize to the mitotic spindle poles during metaphase. (B) During S-phase, WDR62 and ASPM can be detected between each centriole pair in scrambled control (SC) transfected cells. (C) Top: WDR62 antibody specifically detects endogenous WDR62 by Western in scrambled control (SC) transfected cells; signal decreases upon knockdown with siRNAs *WDR62 #1* and *WDR62 #2*. Bottom: VTKR peptide antibody specifically detects endogenous ASPM by Western in scrambled control (SC) transfected cells; signal decreases upon knockdown with siRNAs *ASPM #1* and *ASPM #2*. The asterisk represents the specific band. (D) Both WDR62 and ASPM localize to the mother centriole in interphase cells. Top: HeLa cell co-stained for Centrin (to label centrioles), endogenous WDR62 and CEP164 (to label the mother centriole). Bottom: HeLa cell co-stained for Centrin (to label centrioles), endogenous ASPM and CEP164 (to label the mother centriole). (E) Schematic of the centrosome composed of two centrioles (green), including the mother centriole marked with distal appendages (blue) and the daughter centriole (unmarked), connected by a linker (black). WDR62 and ASPM both localize to the proximal end of the mother centriole (red cloud). (F) Table showing a selected list of hits from the IP-mass-spectrometry screen that meet the threshold for significance (NWD-score > 1) includes ASPM. (G) Co-immunoprecipitation of ASPM with an antibody to endogenous WDR62 confirms the interaction. Left: Lane 1: IgG control IP with c-Myc antibody (SCBT) as a negative control for “stickiness.” Lane 2: IP with antibody to endogenous WDR62. Lane 3: Input (lysate). Right, lane 2: Immunoprecipitation of ASPM confirmed the reciprocal co-precipitation of WDR62. (H) Centrosomal localization of ASPM is dependent on WDR62. ASPM localizes to centrosomes in scrambled control (SC) transfected cells but is absent from centrosomes in cells depleted of WDR62. Insets: c = Centrin and a = ASPM. (I) Centrosomal localization of WDR62 is not dependent on ASPM. WDR62 levels at the centrosome were unchanged in cells treated with scrambled control (SC) or *ASPM* siRNA (*ASPM #2*). Insets: c = Centrin; w = WDR62. See also Supplemental Figure S4.

**Figure 5. WDR62 and ASPM assemble at the centrosome in a sequential hierarchy mediated by CEP63**
(A) Table showing a selected list of interactors from an IP-mass-spectrometry screen, with the number of peptides and percent coverage, suggests that CPAP and CEP63 interact with ASPM. (B) Reciprocal co-immunoprecipitation (IP) of endogenous ASPM, WDR62 and CEP63 demonstrates that they form a 3-protein complex. Lanes 1, 3 and 5: IgG control IP with c-Myc antibody (SCBT) as a negative control. Lanes 2, 4 and 6: IP with antibodies to endogenous CEP63, WDR62 and ASPM, respectively. Rows (top to bottom): Western blot for ASPM, WDR62 and CEP63. (C) RNAi knockdown of *CEP63* blocks the ability of WDR62 to bind ASPM, without changes in protein levels of WDR62 or ASPM. Left: Lane 1 “SC” indicates scrambled control lysate. Lane 2 shows *CEP63* RNAi knockdown lysate. Rows, from top to bottom: Western blot for ASPM, WDR62 and CEP63. Actin served as a loading control. The band marked with an asterisk (*) is specific to CEP63. Right: Lanes 1 and 3 show scrambled control (SC) lysate, Lanes 2 and 4 show *CEP63* RNAi knockdown lysate. Lanes 1–2: IgG control IP. Lanes 3–4: IP with WDR62 antibody. Row 1: Western blot for ASPM. Row 2: Western blot for WDR62. (D) Wdr62 is required for centrosomal localization of Cep63. Wild-type (WT) and *Wdr62 −/−* mouse embryonic fibroblasts (MEFs) stained with Centrin (green), to mark centrioles, and Cep63 (red). Insets: c = Centrin and 3 = Cep63. (E) Quantification of mean Cep63 immunofluorescence intensity across a fixed area, averaged across both centrosomes with background fluorescence subtracted, in WT and *Wdr62 −/−* MEFs. Mean ± SEM. **** p < 0.0001. (F) Centrosomal localization of ASPM is dependent on CEP63. ASPM localizes to centrosomes in scrambled control (SC) transfected cells but is absent from centrosomes in cells depleted of CEP63. Insets: c = Centrin and a = ASPM. (G) CEP63 localization does not depend on ASPM. CEP63 levels at the centrosome were unchanged in cells treated with scrambled control (SC) or *ASPM* siRNA (*ASPM #2*). Insets: c = Centrin; 3 = Cep63. See also Supplemental Figure S5.

**Figure 6. Microcephaly-associated proteins cooperate additively to recruit CPAP/Sas-4 to the centrosome**
(A) IP of endogenous ASPM followed by Western blot with an antibody to CPAP confirms that ASPM interacts with CPAP. (B) IP of endogenous CPAP followed by Western blot with an antibody to ASPM confirms reciprocal interaction of CPAP and ASPM. (C) ASPM is required to localize CPAP to the centrosome. Cells were treated with scrambled control (SC) or *ASPM* siRNAs (*ASPM #2*) and then stained for CPAP. CPAP was practically absent from the centrosomes in ASPM-depleted cells. Insets: c = Centrin; p = CPAP. (D) ASPM localization does not depend on CPAP. Cells were treated with scrambled control (SC) or *CPAP* siRNA and then stained for ASPM. ASPM localization was unchanged in CPAP-depleted cells. Insets: c = Centrin; a = ASPM. (E) Mouse embryonic fibroblasts (MEFs) stained with Centrin (green) to mark centrioles and CPAP (red), showing that *Wdr62* and *Aspm* cooperate in a dose-dependent manner to localize CPAP to the centrosome. Top row, left to right: Wild-type (WT), *Aspm +/−, Wdr62 +/−, Wdr62 +/−, Aspm +/−*. Bottom row, left to right: *Aspm −/−, Wdr62 +/−; Aspm −/−, Wdr62 −/−, Wdr62 −/−; Aspm +/−*. Insets (in grayscale): c = Centrin; p = CPAP. (F) Quantification of CPAP relative immunofluorescence intensity in MEFs of various genotypes: Wild-type (WT), *Aspm +/−, Wdr62 +/−, Wdr62 +/−, Aspm +/−, Aspm −/−, Wdr62 +/−; Aspm −/−, Wdr62 −/−* and *Wdr62 −/−; Aspm +/−*. Mean ± SEM. * p < 0.05 and **** = p < 0.0001 (vs. WT). (G) RNAi knockdown of WDR62 (left) or ASPM (right) does not affect CPAP levels. (H) Model of sequential recruitment of microcephaly-associated proteins to the centrosome: WDR62, followed by CEP63, ASPM and CPAP, respectively. All are required for centriole biogenesis.

**Figure 7. Loss of *Wdr62* and *Aspm* disrupts apical complex proteins and leads to premature dissociation of ciliary remnants from centrosomes**
(A) Reduction in centrosomes and cilia in the *Wdr62* −/− mouse brain, both at and away from the ventricular surface, along with an increase in dissociated ciliary remnants. Shown here are E12.5 WT (top) and *Wdr62 −/−* (bottom) brain sections immunostained for γ-tubulin (centrosomes) and Arl13b (cilia). Arrows denote cilia located away from the ventricular surface, while arrowheads mark non-centrosomal Arl13b (dissociated ciliary remnants). Scale bar = 5 µm. (B) Quantification of centrosomal versus non-centrosomal Arl13b in WT, *Wdr62 −/−* and *Wdr62 −/−; Aspm +/−* brains. Fisher’s exact test, ** p = 0.002 for WT vs. *Wdr62 −/−* and ** p = 0.009 for WT vs. *Wdr62 −/−; Aspm +/−*. (C–D) Loss-of-function of *Wdr62, Aspm* or both severely disrupts apical complex proteins Pals1 and aPKCζ in a dose-dependent manner. From top to bottom: WT, *Wdr62 +/−, Aspm −/−, Wdr62 +/−; Aspm −/−* and *Wdr62 −/−* brains at E14.5 stained for (C) Pals1 and (D) aPKCζ to label the apical complex, and counterstained with DAPI. Scale bar = 50 µm.

See this image and copyright information in PMC

References

1. Atwood SX, Li M, Lee A, Tang JY, Oro AE. GLI activation by atypical protein kinase C iota/lambda regulates the growth of basal cell carcinomas. Nature. 2013;494:484–488. - PMC - PubMed
1. Bilguvar K, Ozturk AK, Louvi A, Kwan KY, Choi M, Tatli B, Yalnizoglu D, Tuysuz B, Caglayan AO, Gokben S, et al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature. 2010;467:207–210. - PMC - PubMed
1. Bogoyevitch MA, Yeap YY, Qu Z, Ngoei KR, Yip YY, Zhao TT, Heng JI, Ng DC. WD40-repeat protein 62 is a JNK-phosphorylated spindle pole protein required for spindle maintenance and timely mitotic progression. J Cell Sci. 2012;125:5096–5109. - PMC - PubMed
1. Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF, et al. ASPM is a major determinant of cerebral cortical size. Nat Genet. 2002;32:316–320. - PubMed
1. Bond J, Roberts E, Springell K, Lizarraga SB, Scott S, Higgins J, Hampshire DJ, Morrison EE, Leal GF, Silva EO, et al. A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet. 2005;37:353–355. - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Molecular Biology Databases
- GlyGen glycoinformatics resource
- Mouse Genome Informatics (MGI)
Research Materials
- Addgene Non-profit plasmid repository

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate

Affiliations

Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate

Authors

Affiliations

Abstract

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases

Research Materials