The intermediate mesoderm is a distinct cell layer within the early developing vertebrate embryo. It is one of the three main divisions of the mesoderm, the middle germ layer, which forms during gastrulation. This mesodermal region plays a role in forming organ systems such as the urogenital system, including the kidneys and associated ducts, and contributes to parts of the circulatory system. Its organized structure allows it to differentiate into specialized precursor cells that form structures like the nephrogenic cords.
Origin within Embryonic Development
The intermediate mesoderm arises from the unsegmented mesoderm during gastrulation, where the three primary germ layers are established. It occupies a specific position within the developing embryo, situated between the paraxial mesoderm (which forms somites) and the lateral plate mesoderm (which gives rise to the heart and blood vessels). This region forms as a distinct column or cord of cells. Its formation is influenced by various signaling pathways, including bone morphogenic proteins (BMPs) and Vg1/Nodal signaling, which help specify growth along the embryo’s dorsoventral axis.
Formation of the Kidneys
The kidneys form from the intermediate mesoderm through a sequential development of three distinct types: the pronephros, mesonephros, and metanephros.
The pronephros is the earliest and most rudimentary kidney structure, appearing around day 22 in humans. While it largely degenerates, its formation lays the groundwork for subsequent kidney structures. The pronephric duct extends caudally, inducing the formation of the mesonephros.
The mesonephros develops caudal to the pronephros, functioning as a temporary kidney between the 6th and 10th weeks of human embryonic life. It consists of mesonephric tubules that connect to the mesonephric (Wolffian) duct. Although the mesonephros largely regresses by week 16, the mesonephric duct persists and is crucial for the development of the definitive adult kidney.
The metanephros, precursor to the adult kidney, begins to form around the fifth week of gestation. It arises from two main components: the ureteric bud, an outgrowth from the caudal mesonephric duct, and the metanephric mesenchyme, a condensation of intermediate mesoderm.
Reciprocal interactions between the ureteric bud and the metanephric mesenchyme drive the development of the adult kidney. The ureteric bud undergoes extensive branching to form the collecting ducts, renal pelvis, and calyces.
The metanephric mesenchyme differentiates into the nephrons, including the glomeruli, proximal tubules, loops of Henle, and distal convoluted tubules. All nephrons are typically formed by 32 to 36 weeks of gestation.
Development of the Reproductive Organs
The intermediate mesoderm also contributes to the formation of the gonads (testes and ovaries) and their associated duct systems.
Initially, indifferent gonads form as genital ridges, longitudinal structures derived from the intermediate mesoderm and overlying epithelium. These ridges initially lack germ cells, which begin to migrate from the yolk sac to the genital ridges around the fourth week.
Once germ cells reach the genital ridges, the epithelium proliferates and penetrates the intermediate mesoderm, forming primitive sex cords. The combination of these germ cells and primitive sex cords forms the indifferent gonad, which can develop into either testes or ovaries.
In male embryos, the SRY gene on the Y chromosome directs the primitive sex cords to form testis cords. Leydig cells, derived from the intermediate mesoderm, begin producing testosterone around the eighth week, driving the differentiation of male internal and external genitalia. The mesonephric ducts develop into structures like the epididymis, vas deferens, and seminal vesicles, while paramesonephric ducts degenerate.
In female embryos, in the absence of the SRY gene, the primitive sex cords develop into ovarian structures. Primordial germ cells within the developing ovaries undergo mitosis, increasing in number. The paramesonephric ducts develop into the fallopian tubes, uterus, and upper vagina. The mesonephric ducts largely regress, leaving only remnants.
Other Structures Derived from Intermediate Mesoderm
Beyond the kidneys and reproductive organs, the intermediate mesoderm also gives rise to other structures, including the adrenal cortex.
The adrenal glands develop from two distinct embryological tissues: the medulla from neural crest cells and the cortex from the intermediate mesoderm.
The adrenal cortex forms from a thickening of the coelomic epithelium, derived from the intermediate mesoderm, located between the urogenital ridge and the dorsal mesentery. This initial thickening forms the adrenogonadal primordium, containing progenitor cells for both the adrenal cortex and gonads.
Cells from this primordium delaminate and invade the underlying mesenchyme to form the adrenal cortex. The adrenal cortex produces steroid hormones like cortisol and aldosterone, playing a role in maintaining homeostasis.