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. 2019 Sep 11;10:4112. doi: 10.1038/s41467-019-12013-y

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — C11orf46 is a neuronal nuclear protein important for callosal development. a (top) Genomic map of chr. 11 WAGR deletion locus. (A–F) Representative sagittal T1 MRI images from midline were shown. A) 8-year-old male control; B) 8-year-old male isolated PAX6+/−; C) 7-year-old male heterozygous 11p13 deletion with PAX6+/− and C11orf46+/−; D) 24-year-old female control; E) 24-year-old female isolated PAX6+/−; F) 25-year-old female heterozygous 11p13 deletion with PAX6+/− and C11orf46+/−. b Hypoplastic corpus callosum (CC) in patients with 11p13 deletion encompassing C11orf46. ANCOVA including age and sex as covariates, compared CC volumes of control (n = 23), isolated PAX6+/− (n = 12), and heterozygous 11p13 deletion with PAX6+/− and C11orf46+/− (n = 27). P-values are shown from two-sided post hoc LSD comparisons: **P < 0.01, ***P < 0.001. Box and whisker plots represent the distribution of unadjusted CC volume. The inner bar indicates median value. The upper and lower box ends represent first and third quantile. The upper and lower whisker ends represent the maximum and minimum values. c C11orf46 protein in mouse cortices at embryonic day 15 (E15) and postnatal day 0 (P0). d mRNA expression of C11orf46 in the mouse cerebral cortex during prenatal and postnatal development (mean ± SEM). n = 3. e (Left) C11orf46 mRNA (red) is predominantly expressed in the cortical plate (CP) in the somatosensory cortex at P0. (Right) C11orf46 protein (red) is predominantly expressed in the CP at P0. Blue, nucleus. Scale bar, 50 µm. MZ, marginal zone; SVZ, subventricular zone. f C11orf46 (red) is expressed in the cytoplasm, but not in the nucleus in Nestin-, PAX6-, and TBR2-positive cells, whereas C11orf46 is expressed in the cytoplasm and in the nucleus with a punctate pattern in TBR1-, NeuroD2-, SATB2-, CUX1-, and CTIP2-positive neuronal cells. (bottom left) Cell type specific C11orf46 expression are summarized in the table. Scale bar, 10 and 100 μm (low magnification images). g Representative images of C11orf46 protein staining with cell type-specific markers (white arrowheads) at P14. C11orf46 is predominantly expressed in CaMKII-positive neurons, but not Olig2 (oligodendrocyte), ALDH1L1 (astrocyte), Iba-1 (microglia) -positive cells. Scale bar, 20 μm