The development of the digestive system in the human embryo 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 Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word � ...

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 mes ...

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 Emb ...

. Different regions of the gut tube such as the

esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to t ...

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

duodenum The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...

, 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 of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

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 gast ...

and its surrounding mesoderm.

Hox genes Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the co ...

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

organization of the gut and its derivatives. The gut system extends from the

oropharyngeal The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...

membrane to the cloacal membrane and is divided into the

foregut The foregut is the anterior part of the alimentary canal, from the mouth to the duodenum at the entrance of the bile duct. Beyond the stomach, the foregut is attached to the abdominal walls by mesentery. The foregut arises from the endoderm, devel ...

, midgut, 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 ju ...

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 fold become elevated, ...

, which is a fold of one of the layers of the

trilaminar germ disc A trilaminar embryonic disc (or trilaminary blastoderm, or trilaminar germ disk) is an early stage in the development of triploblastic organisms, which include humans and many other animals. It is the next stage from the earlier bilaminar embryo ...

, 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 t ...

, appears. This layer elevates and closes

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

, 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

, holds the tubes together and the lateral plate mesoderm, 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 refer to: Healthcare *Lateral (anatomy), an anatomical direction * Lateral cricoarytenoid muscle * Lateral release (surgery), a surgical procedure on the side of a kneecap Phonetics *Lateral co ...

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 is a membrane that closely covers the human and various other embryos when first formed. It fills with amniotic fluid, which causes the amnion to expand and become the amniotic sac that provides a protective environment for the develo ...

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

umbilical cord In 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 is physiologi ...

, which connects the fetus with the

placenta The placenta 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 the physically separate mate ...

. 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 ...

, a congenital defect in the anterior abdominal wall through which the abdominal contents freely protrude. Another possibility is bladder exstrophy, 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, pleural space, or interpleural space is the potential space between the pleurae of the pleural sac that surrounds each lung. A small amount of serous pleural fluid is maintained in the pleural cavity to enable lubrication b ...

, and pericardial cavities. The visceral layer will form the visceral layer of the

serous membranes The serous membrane (or serosa) is a smooth tissue membrane of mesothelium lining the contents and inner walls of body cavities, which secrete serous fluid to allow lubricated sliding movements between opposing surfaces. The serous membrane t ...

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 mes ...

, 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 contains many organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roof is th ...

, forms in the gut layers and in places

mesenteries In zoology, a mesentery is a membrane inside the body cavity of an animal. The term identifies different structures in different phyla: in vertebrates it is a double fold of the peritoneum enclosing the intestines; in other organisms it forms com ...

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 Caudal may refer to: Anatomy * Caudal (anatomical term) (from Latin ''cauda''; tail), used to describe how close something is to the trailing end of an organism * Caudal artery, the portion of the dorsal aorta of a vertebrate that passes into the ...

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.

Diaphragm and thoracic cavity

The

diaphragm Diaphragm may refer to: Anatomy * Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen * Pelvic diaphragm or pelvic floor, a pelvic structure * Urogenital diaphragm or triangular ligament, a pelvic structure Other * Diap ...

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, and ...

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. There ...

and the

. It develops from four components: the septum transversum (central tendon), the

pleuroperitoneal Pleuroperitoneal is a term denoting the pleural and peritoneal serous membranes or the cavities they line. It is divided from the pericardial cavity The pericardium, also called pericardial sac, is a double-walled sac containing the heart an ...

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 embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide ...

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 motor/sensory nerve which 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. ...

, 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 cells, 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 is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. Various types of hernias can occur, most commonly involving the abdomen, and specifically the groin. Groin hernia ...

). 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 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 (plural ''allantoides'' or ''allantoises'') is a hollow sac-like structure filled with clear fluid that forms part of a developing amniote's conceptus (which consists of all embryonic and extraembryonic tissues). It helps the embryo ...

enters the anterior region (future

urogenital sinus The urogenital sinus is a part of the human body only present in the development of the urinary and reproductive organs. It is the ventral part of the cloaca, formed after the cloaca separates from the anal canal during the fourth to seventh w ...

). 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 A proctodeum is the back ectodermal part of an alimentary canal. It is created during embryogenesis by a folding of the outer body wall. It will form the lower part of the anal canal, below the pectinate line The pectinate line (dentate line) i ...

. Ectoderm, in the region of the proctodeum on the surface of part of the cloaca, proliferates and

invaginate Invagination is the process of a surface folding in on itself to form a cavity, pouch or tube. In developmental biology, invagination is a mechanism that takes place during gastrulation. This mechanism or cell movement happens mostly in the vegeta ...

s 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

atresia Atresia is a condition in which an orifice or passage in the body is (usually abnormally) closed or absent. Examples of atresia include: *Aural atresia, a congenital deformity where the ear canal is underdeveloped. * Biliary atresia, a condition i ...

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

, 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 every ...

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 The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previous ...

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