(45) Pluripotency Pathways: How Sox Paralogues Compensate and Collaborate in Early Embryonic Development in Mice

Farina Aziz¹; Jaehwan Kim²; Jason G. Knott²; Amy Ralston³

¹Cell and Molecular Biology Program, Michigan State University, Michigan, East Lansing, MI 48824, USA

²Developmental Epigenetics Laboratory, Department of Animal Science, Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI 48824, USA

³Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA

Abstract Text:

Preimplantation development in mammals, marked by a series of precisely orchestrated molecular events from fertilization to uterine implantation, provides an excellent model for studying the initiation of pluripotency. During murine preimplantation, SOX2 is the earliest marker of pluripotency, labeling pluripotent inside cells as early as the 16-cell stage, when other pluripotency factors such as OCT4 and NANOG are expressed in both pluripotent and non-pluripotent cell types. However, Sox2 is dispensable for formation of the pluripotent epiblast cells in the blastocyst, suggesting that other SOX factors could compensate for the loss of Sox2 during blastocyst formation. We have discovered that the closely related Sox paralogues, Sox15 and Sox21 are reproducibly detected at both the mRNA and protein level alongside Sox2 during preimplantation development. Moreover, Sox15 and Sox21 mRNA and protein are retained in Sox2 null embryos. We found that, like Sox2, neither Sox15 nor Sox21 rely on expression of NANOG and OCT4. Moreover, like Sox2, regulation of Sox21 is dependent on TFAP2C. However, unlike Sox2, expression of Sox15/21 does not rely on HIPPO pathway transcription factor TEAD4. These data suggest that multiple independent pathways regulate the initiation of pluripotency in mice. Moreover, using genetic (knock-out models) and genomic analysis (CUT&RUN, RNA-seq), we aim to characterize the roles of Sox15 and Sox21 in preimplantation lineage decisions. These will advance our understanding of the factors that contribute to the establishment and maintenance of mammalian pluripotency during the very early stages of embryonic development and may further our knowledge on the pathways involved in early embryo viability. This work is supported by NIH R01 HD108722 awarded to A.R.