Control of Oocyte Reawakening by Kit

Hatice Duygu Saatcioglu, Ileana Cuevas, Diego H. Castrillon

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In mammals, females are born with finite numbers of oocytes stockpiled as primordial follicles. Oocytes are “reawakened” via an ovarian-intrinsic process that initiates their growth. The forkhead transcription factor Foxo3 controls reawakening downstream of PI3K-AKT signaling. However, the identity of the presumptive upstream cell surface receptor controlling the PI3K-AKT-Foxo3 axis has been questioned. Here we show that the receptor tyrosine kinase Kit controls reawakening. Oocyte-specific expression of a novel constitutively-active KitD818V allele resulted in female sterility and ovarian failure due to global oocyte reawakening. To confirm this result, we engineered a novel loss-of-function allele, KitL. Kit inactivation within oocytes also led to premature ovarian failure, albeit via a contrasting phenotype. Despite normal initial complements of primordial follicles, oocytes remained dormant with arrested oocyte maturation. Foxo3 protein localization in the nucleus versus cytoplasm explained both mutant phenotypes. These genetic studies provide formal genetic proof that Kit controls oocyte reawakening, focusing future investigations into the causes of primary ovarian insufficiency and ovarian aging.

Original languageEnglish (US)
Article numbere1006215
JournalPLoS Genetics
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2016

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Oocytes
phenotype
allele
oocytes
sterility
cytoplasm
maturation
mammal
Primary Ovarian Insufficiency
protein
phosphatidylinositol 3-kinase
Phosphatidylinositol 3-Kinases
Alleles
Forkhead Transcription Factors
Female Infertility
alleles
Phenotype
receptors
female fertility
Receptor Protein-Tyrosine Kinases

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Control of Oocyte Reawakening by Kit. / Saatcioglu, Hatice Duygu; Cuevas, Ileana; Castrillon, Diego H.

In: PLoS Genetics, Vol. 12, No. 8, e1006215, 01.08.2016.

Research output: Contribution to journalArticle

Saatcioglu, Hatice Duygu ; Cuevas, Ileana ; Castrillon, Diego H. / Control of Oocyte Reawakening by Kit. In: PLoS Genetics. 2016 ; Vol. 12, No. 8.
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