Abstract
HOX genes are a group of evolutionarily conserved genes that encode a family of transcription factors that regulate early developmental morphogenetic processes and continue to be expressed into adulthood. These highly conserved HOX factors play an unquestioned crucial role as master regulators during embryonic vertebrate development and morphogenesis by controlling the three dimensional body plan organization. HOX genes specify regions of the body plan of an embryo along the head-tail axis. They encode proteins that specify the characteristics of ‘position’, ensuring that the correct structures form in the correct places of the body. Expression of HOX is known to persist in many tissues in the postnatal period suggesting the role of these genes not only during development but also for the functioning of tissues throughout life. The tissue-specific pattern of HOX gene expression is inherent in stromal/stem cells of mesenchymal origin, such as mesenchymal stromal cells, fibroblasts, smooth muscle cells, and preadipocytes, enabling them to memorize their topographic location in the form of their HOX code and to fulfill their location-specific functions. In this chapter, we focus on the expression and potential role of HOX genes in adult tissues. We review evidence that site-specific expression of HOX genes is connected to location-specific disease susceptibility and review studies showing that dysregulated expression of HOX genes can be associated with various diseases. By recognizing the importance of site-specific molecular mechanisms in the organ stroma, we gain new insights into the processes underlying the site-specific manifestation of disease.
Highlights
In vertebrate animals, the stromal compartment of organs is composed of extracellular matrix and mesenchymal cells
Fibroblasts are one of the most abundant and principal stromal cell types and have a variety of vital, locally specialized functions in tissue repair and homeostasis. They are the main source of extracellular matrix (ECM) proteins, which, in addition to providing a structural scaffold for cells, play critical roles in determining cell phenotype and function
Fibroblasts produce and secrete all components of the ECM, including structural proteins, adhesive proteins, and a space-filling ground substance composed of glycosaminoglycans and proteoglycans [1]
Summary
The stromal compartment of organs is composed of extracellular matrix and mesenchymal cells. Fibroblasts are one of the most abundant and principal stromal cell types and have a variety of vital, locally specialized functions in tissue repair and homeostasis. They are the main source of extracellular matrix (ECM) proteins, which, in addition to providing a structural scaffold for cells, play critical roles in determining cell phenotype and function. During development of multicellular organisms, developmental control genes are critical for pattern formation and cell fate specification in specific spatiotemporal patterns [5] Most of these genes encode transcription factors acting in cascades and networks, regulating the expression of further developmental control genes and organ-specific ‘effector’ genes, which control patterning, morphogenesis and differentiation of tissue-specific functions and specific body parts [6]. Functional diversity of fibroblasts is important during embryonic developmental and physiologic specialization of many tissues, but might influence site- and organ-specific differences in the susceptibility of different tissues to disease development [11, 12]
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