The development of the digestive system in the

human embryo Human embryonic development or human embryogenesis is the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of deve ...

concerns the epithelium of the

digestive system The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion (the tongue, salivary glands, pancreas, liver, and gallbladder). Digestion involves the breakdown of food into smaller and smaller compone ...

and the

parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

of its derivatives, which originate from the endoderm. Connective tissue, muscular components, and

peritoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...

components originate in the

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...

. Different regions of the

gut tube The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

such as the

esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...

stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

duodenum The duodenum is the first section of the small intestine in most vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption. The duodenum precedes the jejunum and ileum and is the shortest p ...

, etc. are specified by a retinoic acid gradient that causes

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

s unique to each region to be expressed. Differentiation of the gut and its derivatives depends upon reciprocal interactions between the gut

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gastr ...

and its surrounding mesoderm. Hox genes in the mesoderm are induced by a

Hedgehog signaling pathway The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathwa ...

secreted by gut endoderm and regulate the craniocaudal organization of the gut and its derivatives. The gut system extends from the oropharyngeal membrane to the cloacal membrane and is divided into the

foregut The foregut in humans is the anterior part of the alimentary canal, from the distal esophagus to the first half of the duodenum, at the entrance of the bile duct. Beyond the stomach, the foregut is attached to the abdominal walls by mesentery. ...

midgut The midgut is the portion of the human embryo from which almost all of the small intestine and approximately half of the large intestine develop. After it bends around the superior mesenteric artery, it is called the "midgut loop". It comprises ...

, and

hindgut The hindgut (or epigaster) is the posterior ( caudal) part of the alimentary canal. In mammals, it includes the distal one third of the transverse colon and the splenic flexure, the descending colon, sigmoid colon and up to the ano-rectal junct ...

Body cavities

At the end of the third week, the

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, ...

, which is a fold of one of the layers of the trilaminar germ disc, called the

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...

, appears. This layer elevates and closes

dorsally Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position provi ...

, while the gut tube rolls up and closes ventrally to create a "tube on top of a tube." The

, which is another layer of the trilaminar germ disc, holds the tubes together and the

lateral plate mesoderm The lateral plate mesoderm is the mesoderm that is found at the periphery of the embryo. It is to the side of the paraxial mesoderm, and further to the axial mesoderm. The lateral plate mesoderm is separated from the paraxial mesoderm by a narrow r ...

, the middle layer of the germ disc, splits to form a visceral layer associated with the gut and a parietal layer, which along with the overlying ectoderm, forms the

lateral Lateral is a geometric term of location which may also refer to: Biology and healthcare * Lateral (anatomy), a term of location meaning "towards the side" * Lateral cricoarytenoid muscle, an intrinsic muscle of the larynx * Lateral release ( ...

body wall. The space between the visceral and parietal layers of lateral plate mesoderm is the primitive body cavity. When the lateral body wall folds, it moves ventrally and fuses at the midline. The body cavity closes, except in the region of the connecting stalk. Here, the gut tube maintains an attachment to the yolk sac. The yolk sac is a membranous sac attached to the embryo, which provides nutrients and functions as the circulatory system of the very early embryo. The lateral body wall folds, pulling the

amnion The amnion (: amnions or amnia) is a membrane that closely covers human and various other embryos when they first form. It fills with amniotic fluid, which causes the amnion to expand and become the amniotic sac that provides a protective envir ...

in with it so that the amnion surrounds the embryo and extends over the connecting stalk, which becomes the

umbilical cord In Placentalia, placental mammals, the umbilical cord (also called the navel string, birth cord or ''funiculus umbilicalis'') is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord i ...

, which connects the fetus with the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

. If the ventral body wall fails to close, ventral body wall defects can result, such as ectopia cordis, a congenital malformation in which the heart is abnormally located outside the thorax. Another defect is

gastroschisis Gastroschisis is a birth defect in which the baby's intestines extend outside of the abdomen through a hole next to the belly button. The size of the hole is variable, and other organs including the stomach and liver may also occur outside the b ...

, a congenital defect in the anterior abdominal wall through which the abdominal contents freely protrude. Another possibility is

bladder exstrophy Bladder exstrophy is a congenital anomaly that exists along the spectrum of the exstrophy-epispadias complex, and most notably involves protrusion of the urinary bladder through a defect in the abdominal wall. Its presentation is variable, ofte ...

, in which part of the urinary bladder is present outside the body. In normal circumstances, the parietal mesoderm will form the parietal layer of serous membranes lining the outside (walls) of the

pleural The pleural cavity, or pleural space (or sometimes intrapleural space), is the potential space between the pulmonary pleurae, pleurae of the pleural sac that surrounds each lung. A small amount of serous fluid, serous pleural fluid is maintained ...

, and pericardial cavities. The visceral layer will form the visceral layer of the serous membranes covering the lungs, heart, and abdominal organs. These layers are continuous at the root of each organ as the organs lie in their respective cavities. The

peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...

, a serum membrane that forms the lining of the

abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contain Organ (anatomy), organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roo ...

, forms in the gut layers and in places mesenteries extend from the gut as double layers of

. Mesenteries provide a pathway for vessels, nerves, and lymphatics to the organs. Initially, the gut tube from the caudal end of the foregut to the end of the hindgut is suspended from the dorsal body wall by dorsal mesentery. Ventral mesentery, derived from the septum transversum, exists only in the region of the terminal part of the esophagus, the stomach, and the upper portion of the duodenum.

Rotation and herniation

In the process of lengthening growth, the intestinal duct

hernia A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ (anatomy), organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal Devel ...

tes and rotates. Herniation (

Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...

, meaning 'rupture') takes place at around 7½ weeks in the

and refers to the retraction of the intestine from the extraembryonal

navel The navel (clinically known as the umbilicus; : umbilici or umbilicuses; also known as the belly button or tummy button) is a protruding, flat, or hollowed area on the abdomen at the attachment site of the umbilical cord. Structure The u ...

coelom The coelom (or celom) is the main body cavity in many animals and is positioned inside the body to surround and contain the digestive tract and other organs. In some animals, it is lined with mesothelium. In other animals, such as molluscs, i ...

into the

abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...

(panel B3). The intestinal duct rotates by 90° (counterclockwise when viewing from tail-to-head) around the body axis (see panel B1) in the same direction as the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

. According to the Axial Twist theory, the rotation is part of a complex twist that involves the entire body in all

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

animals. During this twist, the anterior head region rotates 90° counterclockwise, the body 90° clockwise, but sparing the heart and bowels. Accordingly, the embryo turns on its side. The forebrain becomes turned around with respect to the while the heart and bowels (which do not take part in the twist) become turned counterclockwise with respect to the body. Folding occurs in a typical manner as shown in the diagram (panel B2-3, C). The folding is a result of the elongation of the duct.

Diaphragm and thoracic cavity

The diaphragm divides the

body cavity A body cavity is any space or compartment, or potential space, in an animal body. Cavities accommodate organs and other structures; cavities as potential spaces contain fluid. The two largest human body cavities are the ventral body cavity, a ...

into the

thoracic cavity The thoracic cavity (or chest cavity) is the chamber of the body of vertebrates that is protected by the thoracic wall (rib cage and associated skin, muscle, and fascia). The central compartment of the thoracic cavity is the mediastinum. Ther ...

and the

. It develops from four components: the septum transversum (central tendon), the pleuroperitoneal membranes, the dorsal mesentery of the esophagus, and muscular components from

somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along the head-to-tail axis in segmentation (biology), segmented animals. ...

s at cervical levels three to five (C3–5) of the body wall. Since the septum transversum is located initially opposite cervical segments of three to five, and since muscle cells for the diaphragm originate from somites at these segments, the

phrenic nerve The phrenic nerve is a mixed nerve that originates from the C3–C5 spinal nerves in the neck. The nerve is important for breathing because it provides exclusive motor control of the diaphragm, the primary muscle of respiration. In humans, t ...

, which innervates the diaphragm, also arises from these segments of the spinal cord (C3, 4, and 5). The thoracic cavity is divided into the pericardial cavity and two pleural cavities for the lungs by the pleuropericardial membranes.

Divisions of the gut tube

As a result of the cephalocaudal and lateral folding of the embryo, a portion of the endoderm-lined yolk sac cavity is incorporated into the embryo to form the primitive gut. In the cephalic and caudal parts of the embryo, the primitive gut forms a tube, the foregut and hindgut, respectively. The middle part, the midgut, remains temporally connected to the yolk sac by means of the

vitelline duct In the human embryo, the vitelline duct, also known as the vitellointestinal duct, the yolk stalk, the omphaloenteric duct, or the omphalomesenteric duct, is a long narrow tube that joins the yolk sac to the midgut lumen of the developing fetus. ...

Foregut

The foregut gives rise to the esophagus, the trachea, lung buds, the stomach, and the duodenum proximal to the entrance of the bile duct. In addition, the liver, pancreas, and biliary apparatus develop as outgrowths of the endodermal epithelium of the upper part of the duodenum. Since the upper part of the foregut is divided by the tracheoesophageal septum into the esophagus posteriorly and the trachea and lung buds anteriorly, deviation of the septum may result in abnormal openings between the trachea and esophagus. The epithelial liver cords and biliary system growing out into the septum transversum differentiate into parenchyma. Hematopoietic cells (present in the liver in greater numbers before birth than afterward),

Kupffer cell Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. K ...

s, and connective tissue cells originate in the mesoderm. The pancreas develops from a ventral bud and a dorsal bud that later fuse to form the definitive pancreas. Sometimes, the two parts surround the duodenum ( annular pancreas), causing constriction of the gut.

Midgut

The midgut forms the primary intestinal loop, from which originates the distal duodenum to the entrance of the bile duct. The loop continues to the junction of the proximal two-thirds of the transverse colon with the distal third. At its apex, the primary loop remains temporarily in open connection with the yolk sac through the

. During the sixth week, the loop grows so rapidly that it protrudes into the umbilical cord (physiological

herniation A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal development of the in ...

). In the 10th week, it returns into the abdominal cavity. While these processes are occurring, the midgut loop rotates 270° counterclockwise. Common abnormalities at this stage of development include remnants of the vitelline duct, failure of the midgut to return to the abdominal cavity, malrotation, stenosis, and duplication of parts.

Hindgut

The hindgut gives rise to the region from the distal third of the

transverse colon In human anatomy, the transverse colon is the longest and most movable part of the Large intestine#Structure, colon. Anatomical position It crosses the abdomen from the ascending colon at the right colic flexure (hepatic flexure) with a downward ...

to the upper part of the anal canal. The distal part of the anal canal originates from the ectoderm. The hindgut enters the posterior region of the cloaca (future anorectal canal), and the

allantois The allantois ( ; : allantoides or allantoises) is one of the extraembryonic membranes arising from the yolk sac. It is a hollow sac-like structure filled with clear fluid that forms part of the developing conceptus in an amniote that helps the ...

enters the anterior region (future

urogenital sinus The urogenital sinus is a body part of a human or other Placentalia, placental only present in the development of the urinary system, development of the urinary and development of the reproductive organs, reproductive organs. It is the ventral p ...

). The urorectal septum divides the two regions and breakdown of the cloacal membrane covering this area provides communication to the exterior for the anus and urogenital sinus. The upper part of the anal canal is derived from endoderm of the hindgut. The lower part (one-third) is derived from ectoderm around the proctodeum. Ectoderm, in the region of the proctodeum on the surface of part of the cloaca, proliferates and invaginates to create the anal pit. Subsequently, degeneration of the cloacal membrane establishes continuity between the upper and lower parts of the anal canal. Abnormalities in the size of the posterior region of the cloaca shift the entrance of the anus anteriorly, causing rectovaginal and rectourethral fistulas and atresias.

Molecular regulation

Regional specification of the gut tube into different components occurs during the time that the lateral body folds are bringing the two sides of the tube together. Different regions of the gut tube are initiated by retinoic acid (RA) from the pharynx to the colon. This RA causes transcription factors to be expressed in different regions of the gut tube. Thus, SOX2 specifies the esophagus and stomach; PDX1 specifies the duodenum; CDXC specifies the small intestine; CDXA specifies the large intestine and rectum. The differentiation of the gut and its derivatives depends upon reciprocal interactions between the gut endoderm (epithelium) and its surrounding mesoderm (an epithelial-mesenchymal interaction). Hox genes in the mesoderm are induced by SHH secreted by gut endoderm and regulate the craniocaudal organization of the gut and its derivatives. Once the mesoderm is specified by this code, it instructs the endoderm to form components of the mid- and hindgut regions, such as the small intestine, caecum, colon, and cloaca.

Mesentery

Portions of the gut tube and its derivatives are suspended from the dorsal and ventral body wall by mesenteries, double layers of peritoneum that enclose an organ and connect it to the body wall. Such organs are called intraperitoneal, whereas organs that lie against the posterior body wall and are covered by peritoneum on their anterior surface only are considered retroperitoneal. So, mesenteries are double layers of peritoneum that pass from one organ to another or from an organ to the body wall as a peritoneal ligament. Mesenteries provide pathways for vessels, nerves, and lymphatic structures to and from abdominal viscera. Initially the foregut, midgut, and hindgut are in extensive contact with the

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood, or bone. The interactions between mesenchyme and epithelium help to form nearly ever ...

of the posterior abdominal wall. By the fifth week, the connecting tissue bridge has narrowed, and the caudal part of the foregut, the midgut, and a major part of the hindgut are suspended from the abdominal wall by the dorsal mesentery, which extends from the lower end of the esophagus to the cloacal region of the hindgut. In the region of the stomach, it forms the dorsal mesogastrium or greater omentum. In the region of the duodenum, it forms the dorsal mesoduodenum; and in the region of the colon, it forms the dorsal mesocolon. Dorsal mesentery, of the jejunal and ileal loops, forms the mesentery proper. The ventral mesentery, located in the region of the terminal part of the esophagus, the stomach and the upper part of the duodenum, is derived from the septum transversum. Growth of the liver into the mesenchyme of the septum transversum divides the ventral mesentery into the lesser omentum, extending from the lower portion of the esophagus, the stomach, and the upper portion of the duodenum to the liver and the falciform ligament, extending from the liver to the ventral body wall.

References

{{Development of digestive system Embryology of digestive system