Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly

被引：34

作者：

Journiac, Nathalie ^{[1
,10
]}

Gilabert-Juan, Javier ^{[1
,11
]}

Cipriani, Sara ^{[1
,12
]}

Benit, Paule ^{[1
]}

Liu, Xiaoqian ^{[2
]}

Jacquier, Sandrine ^{[1
]}

Faivre, Valerie ^{[1
]}

Delahaye-Duriez, Andree ^{[1
,3
]}

Csaba, Zsolt ^{[1
]}

Hourcade, Tristan ^{[1
]}

Melinte, Eliza ^{[1
]}

Lebon, Sophie ^{[1
]}

Violle-Poirsier, Celine ^{[4
]}

Oury, Jean-Francois ^{[5
]}

Adle-Biassette, Homa ^{[1
,6
]}

Wang, Zhao-Qi ^{[2
,7
]}

Mani, Shyamala ^{[1
,8
]}

Rustin, Pierre ^{[1
]}

Gressens, Pierre ^{[1
,9
]}

Nardelli, Jeannette ^{[1
]}

机构：

[1] Univ Paris, NeuroDiderot, INSERM, F-75019 Paris, France

[2] FLI, Leibniz Inst Aging, Jena, Germany

[3] Univ Paris 13, Hop Jean Verdier, AP HP, Serv Histol Embryol & Cytogenet,Sorbonne Paris Ci, Bobigny, France

[4] CHU Reims, Serv Genet & Biol Reprod, Reims, France

[5] Hop Robert Debre, AP HP, Serv Gynecol Obstet, Paris, France

[6] Hop Lariboisiere, AP HP, Serv Anat & Cytol Pathol, Paris, France

[7] Friedrich Schiller Univ Jena, Fac Biol & Pharm, Jena, Germany

[8] Curadev Pharma Pvt Ltd, Noida, India

[9] Kings Coll London, St Thomas Hosp, Div Imaging Sci & Biochem Engn, Ctr Dev Brain,Dept Perinatal Imaging & Hlth, London, England

[10] Univ Lille, CHU Lille, INSERM, U1172,LilNCog Lille Neurosci & Cognit, F-59000 Lille, France

[11] Coll France, CNRS, INSERM, U1050,UMR7241, Paris, France

[12] ICAN, IE3M, Paris, France

来源：

CELL REPORTS | 2020年 / 31卷 / 02期

关键词：

OUTER SUBVENTRICULAR ZONE; UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM; PROLIFERATION; PROGENITORS; ADAPTATION; EVOLUTION; DIVISION; GLUCOSE; IMAGE;

D O I：

10.1016/j.celrep.2020.03.070

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

A distinctive feature of neocortical development is the highly coordinated production of different progenitor cell subtypes, which are critical for ensuring adequate neurogenic outcome and the development of normal neocortical size. To further understand the mechanisms that underlie neocortical growth, we focused our studies on the microcephaly gene Mcph1, and we report here that Mcph1 (1) exerts its functions in rapidly dividing apical radial glial cells (aRGCs) during mouse neocortical development stages that precede indirect neurogenesis; (2) is expressed at mitochondria; and (3) controls the proper proliferation and survival of RGCs, potentially through crosstalk with cellular metabolic pathways involving the stimulation of mitochondrial activity via VDAC1/GRP75 and AKT/HK2NDAC1 and glutaminolysis via ATF4/PCK2. We currently report the description of a MCPH-gene implication in the interplay between bioenergetic pathways and neocortical growth, thus pointing to alterations of cellular metabolic pathways, in particular glutaminolysis, as a possible cause of microcephalic pathogenesis.

引用

页数：26

共 65 条

[1] A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels [J].