Chapter 18 Development of the primitive digestive tract commences with the cranial, caudal and lateral foldings of the embryonic disc and the incorporation of the dorsal portion of the primitive yolk sac into the embryo. The endodermally‐lined cranial portion of the tract formed within the head fold is termed the foregut, the part formed within the caudal fold is referred to as the hindgut, while the segment of embryonic endoderm between the foregut and hindgut, which is continuous with the yolk sac, is called the midgut. Progressive folding of the embryo constricts the wide connection between the midgut and yolk sac until only a narrow connection, the vitelline duct, remains between these two structures (Fig 18.1). The blind end of the foregut is apposed to an ectodermal depression in the developing head region, the stomodeum, which later forms the oral cavity. A similar ectodermal depression, in contact with the blind end of the hindgut, the proctodeum, later forms the anus. The ecto‐endodermal membrane, which separates the stomodeum from the foregut, is called the oropharyngeal membrane; the structure between the hindgut and proctodeum is termed the cloacal membrane. As development progresses, both these membranes regress and the oral cavity becomes continuous with the foregut and the hindgut opens to the exterior (Fig 18.2). Two major abdominal organs, the liver and pancreas, arise as outgrowths from the distal region of the foregut. Figure 18.1 Sequential stages in lateral body folding leading to the formation of the abdominal wall, the gut and its associated mesenteries. A. Cross‐section through an embryo prior to the formation of lateral body folds. B. Advanced stage of lateral body folding showing formation of the gut and the vitelline duct. C. Closure of the body wall and positions of the dorsal and ventral mesenteries. D. Atrophy of the ventral mesentery leading to formation of the peritoneal cavity. Figure 18.2 Longitudinal sections through an embryo showing sequential stages in cranial and caudal body‐folding leading to the formation of the foregut, midgut and hindgut (A to C). If abnormalities occur in the processes controlling the formation of the foregut and hindgut early in development, these have fatal consequences. Accordingly, studies on the molecular mechanisms relating to these processes in transgenic mice provide inconclusive information. The transcription factors Foxa1 and Foxa2, GATA‐4 and GATA‐6, which are expressed in endoderm at an early stage in development, are considered to be important in early foregut development. Molecular interactions between the endoderm and the mesoderm are prerequisites for normal alimentary tract development. The Sonic Hedgehog transcription factor, which is expressed in the endoderm of the gut, acts on mesoderm during gut development, inducing Bmp‐4 expression in the splanchnic mesoderm. Expression of Bmp‐4, in turn, contributes to formation of the smooth muscle of the alimentary tract. During organogenesis, tissue morphogenesis and cellular identity are highly coordinated by a range of signalling factors, including Fgf, Bmp, Wnt, Hedgehog and Notch, all of which have stage‐specific roles in endoderm morphogenesis. These stages can be divided into endoderm formation, endoderm patterning, organ specification, organ bud formation and differentiation of organs. While Sox‐17 plays a role in specifying particular regions of the gut tube, there are numerous other factors which contribute to this process, including retinoic acid. The primitive alimentary tract is composed of an inner endodermal lining and an outer layer of splanchnic mesoderm. The epithelium of the digestive tract and its associated glands are derivatives of endoderm while the splanchnic mesoderm gives rise to the smooth muscle and connective tissue of the tract. Subsequently, these tissues become organised into four basic histological layers: mucosa, submucosa, muscularis externa and serosa or adventitia. As the length of the alimentary tract increases, development of the muscularis externa proceeds along the cranial–caudal axis with the inner circular layer appearing first, followed by the outer longitudinal layer. Wide variations, evident in the structure and function of digestive systems of animals, reflect their evolutionary development. These differences apply particularly to structures associated with the prehension, mastication and digestion of food. Carnivores have short, simple gastrointestinal tracts; in contrast, herbivores usually have long, voluminous, compartmentalised digestive tracts. Molecular controls for the differentiation of the tissues and organs of the alimentary tract influence development in the three directional planes, and also radially. There is evidence that homeobox (Hox) genes play an important role in establishing regional development of the alimentary tract along the cranial–caudal axis of the embryo. Hox genes are expressed in nested overlapping patterns along the cranial–caudal axis (Fig 18.3). At defined regions of demarcation, sphincters of different size develop under the influence of a combination of homeobox genes together with other genes including Nkx‐2.5. Several Hox genes are required for the specification of the pyloric, ileo‐caecal and anal sphincters. The formation of sphincters seems to coincide with large shifts in Hox gene expression patterns. Along the cranial–caudal axis, expression of paralogous groups of Hox genes in defined anatomical regions in a cranial–caudal direction corresponds to the 3′ to 5′ location of these genes within their respective gene clusters. As an example, Hox‐12 and Hox‐13 are expressed in the caudal regions of the developing gut and are located on the 5′ end of their respective chromosomes. Figure 18.3 Regions of Hox gene expression in endodermally‐derived and mesodermally‐derived tissues along the cranial–caudal axis of the developing alimentary tract. In early alimentary tract development, there is uniformity along the dorsal–ventral axis and Shh is expressed diffusely and uniformly. Later, in defined regions where active budding occurs, expression of Shh is inhibited. Ventral specification of the foregut, which is required for organogenesis of the thyroid gland and the lung, involves the transcription factor Nkx‐2.1. Within a given species, the alimentary tract exhibits a consistent arrangement along the left–right axis of the body. Expression of Shh on the left side during early embryonic development results in the unilateral upregulation of other factors such as Nodal, Pitx‐2, Nkx‐3.2 and Fgf‐8 which are expressed exclusively on the left side of the embryo. Despite the fact that the overall controls for left–right orientation are similar, it has been suggested that each organ responds to these signals independently. The precise mechanisms which regulate organ‐specific responses are unknown. The cytodifferentiation of the endodermal lining along the length of the alimentary tract is strongly influenced by specific mesodermally‐derived factors in each defined region. Hence, the characteristics of the epithelium are specific for a given region along the length of the alimentary tract. Despite these regional differences, a cross‐section through any region of the alimentary tract exhibits radial organisation from serosa to lumen. Early differentiation events which influence the pattern of radial development involve a number of signalling molecules including Shh. As villi and glands develop and the cells in these regions become increasingly differentiated, Shh expression decreases. The oesophagus, which at first is a short tube, extends from the tracheal groove to the fusiform dilation of the foregut, the primordial stomach. In association with the elongation of the cervical region of the embryo, the oesophagus increases in length. Along its length, the endoderm of the oesophagus is surrounded by somatic mesoderm of the head, which develops into striated muscle. Species variation is evident in the extent to which the oesophagus is invested with skeletal muscle. In ruminants, the muscular component consists entirely of striated muscle. With the exception of a short terminal portion where the inner circular muscle layer is composed of smooth muscle, oesophageal muscle in carnivores is skeletal. In the porcine oesophagus, a short region near the stomach is composed of smooth muscle, while in horses and cats the smooth muscle extends over the caudal third of the oesophagus. In the early stages of development, oesophageal epithelium is columnar. Later, this epithelium becomes stratified and squamous in all species, with keratinisation evident in herbivores. Oesophageal glands, which develop from the epithelium, are located in the submucosal layer. In domestic animals, these branched, tubulo‐alveolar mucous glands vary in their distribution along the length of the oesophagus. The stomach, which can be recognised early in embryological development as a fusiform dilation of the caudal part of the foregut, is attached to the dorsal abdominal wall by the dorsal mesogastrium and to the ventral wall by the ventral mesogastrium (Fig 18.4). Because the dorsal region of the stomach grows at a greater rate than the ventral region, this organ changes morphologically, resulting in the formation of a dorsal greater curvature and a ventral lesser curvature. Further growth at the cranial aspect of the greater curvature gives rise to the primordium of the fundus of the simple stomach. During its early development, the stomach undergoes two rotations. In the first rotation, the organ moves through an angle of 90° to the left about a cranial–caudal axis, which results in the former left side assuming a ventral position and the former right side a dorsal position. At this stage of development, the stomach is a C‐shaped sac, flattened dorso‐ventrally with greater and lesser curvatures. Subsequent rotation of the stomach through a 45° angle in an anti‐clockwise direction about a dorsal–ventral axis results in its caudal portion occupying a position to the right of the median plane. Consequently, the greater curvature of the stomach is directed to the left and caudally within the abdomen. The anatomical region of the stomach into which the oesophagus opens is referred to as the cardia. The portion which lies above the level of the cardia is called the fundus. The large middle portion of the stomach is termed the body and the most distal area is referred to as the pylorus. Figure 18.4 Lateral view A, and ventro‐lateral views and cross‐sections through the cranial abdominal region of a canine embryo. B. Developing stomach showing position of the dorsal mesogastrium and the ventral mesogastrium. C. Commencement of gastric rotation to the left and the position of the spleen in the dorsal mesogastrium and the liver in the ventral mesogastrium. D. Elongation of the dorsal mesogastrium and formation of the omental bursa. Growth of the liver in the ventral mesogastrium results in the formation of the lesser omentum dorsal to the liver and the falciform ligament ventrally. Evolutionary development accounts, in part, for differences not only in the shape and size but also in the epithelial lining and glandular development of the stomach. In carnivores, horses and pigs, the stomach consists of a single compartment. In contrast with the structure of the canine stomach, the porcine stomach has a conical diverticulum in the fundic region. The fundus of the equine stomach, which extends markedly above the level of the cardia, is large, and is referred to as the saccus caecus or blind sac. In ruminants, the simple gastric primordium gives rise to a four‐chambered structure, termed a complex or ruminant stomach. In domestic animals, the lining of the gastric primordium, which at first is composed of simple columnar epithelium, later exhibits species‐specific regional differences. Simple columnar epithelium persists throughout the carnivore stomach, while in horses and pigs stratified squamous epithelium replaces columnar epithelium in defined gastric regions. In those regions of the stomach where simple columnar epithelium is present, gastric glands develop which extend into the lamina propria of the gastric mucosa. This zone is known as the glandular region as distinct from that area covered by stratified squamous epithelium, which is referred to as the non‐glandular region. The rumen, reticulum and omasum, compartments of the ruminant stomach, are lined by stratified squamous epithelium and, accordingly, are non‐glandular. In contrast, the fourth compartment of the ruminant stomach, the abomasum, which is lined by simple columnar epithelium, contains gastric glands and is physiologically comparable to the simple stomach. Early in evolutionary development, the primary role of the stomach was for food storage. Later, as a consequence of glandular development and the production of digestive enzymes, the stomach acquired a central role in the digestion of food. As the stomach undergoes rotation, the ventral mesogastrium anchoring the stomach, and the dorsal mesogastrium suspending the stomach, also undergo positional changes (Fig 18.4D). The dorsal mesogastrium, which lengthens, becomes displaced to the left side with the stomach and forms a double fold, subsequently called the greater omentum. The cavity enclosed by this double fold is termed the omental bursa. This space communicates with the peritoneal cavity through the epiploic foramen. Modifications in the arrangement of the ventral mesogastrium are described with the development of the liver. The gastric primordium of a 30‐day‐old bovine embryo is a spindle‐shaped structure similar to the gastric primordium of animals with simple stomachs at a comparable stage of development. This primordial structure has a dorsal greater and ventral lesser curvature and undergoes rotation to the left in a manner similar to that which occurs in simple‐stomached animals. The fundic region of the gastric primordium extends cranially and to the left of the median plane. By the 34th day, this cranial expansion, which represents the primordium of the rumen and reticulum, is prominent (Fig 18.5
Digestive system
Molecular regulation of alimentary tract development
Cranial–caudal pattern of development
Dorsal–ventral pattern of development
Positioning of the alimentary tract along the left–right axis of the embryo
Radial development of the alimentary tract
Oesophagus
Stomach
Bovine stomach
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
