MAP3K1 Regulates Female Reproductive Tract Development.
Eiki KimuraMaureen MonganBo XiaoAntonius ChristiantoJingjing WangVinicius S CarreiraBrad BolonXiang ZhangKatherine A BurnsJacek BiesiadaMario MedvedovicAlvaro PugaYing XiaPublished in: Disease models & mechanisms (2024)
Mitogen-Activated Protein 3 Kinase 1 (MAP3K1) has a plethora of cell-type specific functions not yet fully understood. Herein we describe a role for MAP3K1 in female reproductive tract (FRT) development. MAP3K1 kinase domain-deficient female mice exhibit imperforate vagina, labor failure, and infertility. These defects correspond with shunted Müllerian ducts (MDs), the embryonic precursors of FRT, that manifest as contorted caudal vagina and abrogated vaginal-urogenital sinus fusion in neonates. The MAP3K1 kinase domain is required for an optimal activation of the Jun-N-terminal kinase (JNK) and cell polarity in MD epithelium, and for up-regulation of WNT signaling in mesenchyme surrounding the caudal MD. The MAP3K1-deficient epithelial cells and MD epithelium have reduced expression of WNT7B ligands. Correspondingly, conditioned media derived from MAP3K1-competent, but not deficient, epithelial cells activate a TCF/Lef-luciferase reporter in fibroblasts. These observations indicate that MAP3K1 regulates MD caudal elongation and FRT development in part through the induction of paracrine factors in epithelium that trans-activate WNT signaling in mesenchyme.
Keyphrases
- high density
- molecular dynamics
- protein kinase
- stem cells
- tyrosine kinase
- type diabetes
- poor prognosis
- cell proliferation
- signaling pathway
- single cell
- oxidative stress
- crispr cas
- adipose tissue
- mesenchymal stem cells
- metabolic syndrome
- wild type
- long non coding rna
- preterm birth
- extracellular matrix
- insulin resistance