Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly

Nathalie Journiac, Javier Gilabert-Juan, Sara Cipriani, Paule Benit, Xiaoqian Liu, Sandrine Jacquier, Valérie Faivre, Andrée Delahaye-Duriez, Zsolt Csaba, Tristan Hourcade, Eliza Melinte, Sophie Lebon, Céline Violle-Poirsier, Jean-François Oury, Homa Adle-Biassette, Zhao-Qi Wang, Shyamala Mani, Pierre Rustin, Pierre Gressens, Jeannette Nardelli

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19 Citations (Scopus)
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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/HK2/VDAC1 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.

Original languageEnglish
Article number107506
JournalCell Reports
Issue number2
Publication statusPublished - 14 Apr 2020


  • ATF4
  • GRP75
  • PCK2
  • VDAC1


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