Kohoutek, J. | bioRxiv Science

bioRxiv2024

Absence of CDK12 in oocyte leads to female infertility

Transcriptional activity and gene expression are essential for the development of a mature, meiotically competent oocyte. We have found that the absence of cyclin-dependent kinase 12 (CDK12) in oocytes leads to complete female sterility, as there are no fully developed oocytes able to accomplish meiosis I in the ovaries. Mechanistically, CDK12 in growing oocytes controls POLII activity and maintenance of the physiological maternal transcriptome, which negatively affects protein synthesis that promotes further oocyte growth. In addition, disruption of oocyte development disrupts folliculogenesis, resulting in a premature failure phenotype without terminal folliculogenesis and ovulation. In summary, we have characterized a single master regulator of the oocyte transcriptional program and gene expression that is essential for oocyte growth and female fertility. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=113 HEIGHT=200 SRC="FIGDIR/small/622910v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@179b286org.highwire.dtl.DTLVardef@b7a847org.highwire.dtl.DTLVardef@1890a35org.highwire.dtl.DTLVardef@1fd2798_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2023

Early embryogenesis in CHDFIDD mouse model reveals facial clefts and altered craniofacial neurogenesis

Congenital heart defects, facial dysmorphism and intellectual development disorder (CHDFIDD) is associated with mutations in CDK13 gene which encodes a transcription regulating Cyclin-dependent kinase 13 (CDK13). Here we analyzed early embryonic stages of CHDFIDD mouse models with hypomorphic mutation in Cdk13 gene with very similar phenotypic manifestations plus cleft lip/palate and knockout of Cdk13 which exhibits robust phenotype with midfacial cleft. Cdk13 is strongly expressed in the mouse embryonic craniofacial structures, namely in the forebrain, nasal epithelium and maxillary mesenchyme. In vitro, CDK13 protein is located not only in nuclear region but also in the cellular protrusions in cultured mesenchymal cells and cells isolated from dorsal root ganglia. In Cdk13-deficient embryos, we found hypoplastic branches of the trigeminal nerve including maxillary branch and additionally we detected significant gene expression changes of molecules involved in neurogenesis (Mef2c, Pou4f1, Sod1, Cdk5rap2, Nrcam) within the developing palatal shelves. Key palate-associated molecules (Msx1 and Meis2) were downregulated during early craniofacial development in mutant embryos. These results demonstrate the role of CDK13 in regulation of facial morphogenesis and also growth of craniofacial peripheral nerves.

developmental biology↗