Tissue Remodeling in the Female Reproductive Tract—A Complex Process Becomes More Complex: The Role of Hox Genes

Homeobox (Hox/HOX) genes are conserved genes that encode master transcription factors regulating genes that in turn regulate other genes in large networks. They play important roles in organogenesis and morphogenesis during mammalian embryonic growth [1–5]. In mammals, Hox/HOX genes are contained in four clusters: a, b, c, and d. Hox/HOX genes are also expressed in adult cells, where they are associated with extracellular matrix (ECM)-dependent alterations in gene expression and cell phenotype by promoting cell proliferation, cell adhesion, apoptosis, and cell migration [2–4]. These processes themselves depend on the highly dynamic ECM remodeling and rapid transient cell-cell and cell-matrix interactions [6]. Furthermore, expression of specific Hox/HOX genes is influenced by the ECM-cell interactions [6]. In addition to the ECM regulation of these genes, components of the ECM are also targets of Hox/HOX gene regulation [7]. This phenomenon has been called dynamic reciprocity [6]. In mice, Hoxa9, Hoxa10, Hoxa11, and Hoxa13 are expressed in the female reproductive tract [2], and HOXA11 has been shown to promote fibroblast proliferation in the uterosacral ligaments of women [6]. In this current issue of Biology of Reproduction, Yan Ma and colleagues report the development of a mouse model of in vivo Hoxa11 silencing within the female genital tract and abrogate gene effects on interstitial collagens and the gelatinase class of matrix metalloproteinases (MMPs) [7].