Expression of Genes in the 16p11.2 Locus during Development of the Human Fetal Cerebral Cortex.
Expression of Genes in the 16p11.2 Locus during Development of the Human Fetal Cerebral Cortex.
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16p11.2基因在人胎大脑皮层发育过程中的表达
DOI：
10.1093/cercor/bhab067
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发表时间：
2021-07-29
期刊：
影响因子：
--
通讯作者：
Pratt T
中科院分区：
文献类型：
--
作者：
Morson S;Yang Y;Price DJ;Pratt T
593 kbp的16p11.2拷贝数变异（CNV）影响29个蛋白质编码基因的基因剂量，约1%的自闭症谱系障碍（ASD）病例涉及杂合16p11.2微重复或微缺失。16p11.2 CNV经常与大头畸形或小头畸形相关，表明神经发生的早期缺陷可能导致随后的ASD症状，但尚不清楚哪些16p11.2转录物在祖细胞中表达，以及其水平可能影响神经发生。对人胎儿基因表达数据的分析显示，KIF22、ALDOA、HIRIP3、PAGR 1和MAZ转录物在神经祖细胞中表达，与有丝分裂后细胞相比，ALDOA和KIF22显著富集。为了研究ALDOA和KIF22蛋白在人类大脑皮层发育中的可能作用，我们使用免疫组织化学染色来描述它们在第一和第二妊娠早期人类大脑皮层中的表达。KIF22蛋白仅限于增殖细胞，其水平在细胞周期中增加，并在有丝分裂时达到峰值。ALDOA蛋白在所有细胞类型中表达，并且不随细胞周期时相而变化。我们的表达分析表明，在16p11.2 CNV患者中，大脑皮层神经发生的改变有助于ASD的发生。
The 593 kbp 16p11.2 copy number variation (CNV) affects the gene dosage of 29 protein coding genes, with heterozygous 16p11.2 microduplication or microdeletion implicated in about 1% of autism spectrum disorder (ASD) cases. The 16p11.2 CNV is frequently associated with macrocephaly or microcephaly indicating early defects of neurogenesis may contribute to subsequent ASD symptoms, but it is unknown which 16p11.2 transcripts are expressed in progenitors and whose levels are likely, therefore, to influence neurogenesis. Analysis of human fetal gene expression data revealed that KIF22, ALDOA, HIRIP3, PAGR1, and MAZ transcripts are expressed in neural progenitors with ALDOA and KIF22 significantly enriched compared to post-mitotic cells. To investigate the possible roles of ALDOA and KIF22 proteins in human cerebral cortex development we used immunohistochemical staining to describe their expression in late first and early second trimester human cerebral cortex. KIF22 protein is restricted to proliferating cells with its levels increasing during the cell cycle and peaking at mitosis. ALDOA protein is expressed in all cell types and does not vary with cell-cycle phase. Our expression analysis suggests the hypothesis that altered neurogenesis in the cerebral cortex contributes to ASD in 16p11.2 CNV patients.
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影响因子：
4.8
作者：
Buscaglia, CA;Penesetti, D;Nussenzweig, V
通讯作者：
Nussenzweig, V
影响因子：
5.3
作者：
Budday S;Steinmann P;Kuhl E
通讯作者：
Kuhl E
影响因子：
25
作者：
de Anda, Froylan Calderon;Rosario, Ana Lucia;Durak, Omer;Tran, Tracy;Graeff, Johannes;Meletis, Konstantinos;Rei, Damien;Soda, Takahiro;Madabhushi, Ram;Ginty, David D.;Kolodkin, Alex L.;Tsai, Li-Huei
通讯作者：
Tsai, Li-Huei
自闭症中发现的 16p11.2 病变模型的剂量依赖性表型
DOI：
10.1073/pnas.1114042108
发表时间：
2011-10-11
影响因子：
11.1
作者：
Horev, Guy;Ellegood, Jacob;Mills, Alea A.
通讯作者：
Mills, Alea A.
影响因子：
4.8
作者：
Kao, AW;Noda, Y;Saltiel, AR
通讯作者：
Saltiel, AR