Talk:Gastrointestinal Tract Development

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Neural History

  • 1857 Meissner was the first to describe a nerve plexus in the submucosa of the bowel wall.
  • 1864 Auerbach described the myenteric plexus between the longitudinal and circular muscle layers.
  • 1981 LeDouarin describes neural crest contribution to both plexuses.

Peristalsis - Myenteric Plexus

+ Extrinsic parasympathetic cholinergic nerves (vagal and sacral) excite peristalsis and stimulate

- Sympathetic noradrenergic nerves inhibit the transit of gut contents

Coordinated waves of descending inhibition followed by waves of descending excitation

Secretion and Absorption - Submucosal Plexus

2010

Different thymosin Beta 4 immunoreactivity in foetal and adult gastrointestinal tract

PLoS One. 2010 Feb 9;5(2):e9111.

Nemolato S, Cabras T, Cau F, Fanari MU, Fanni D, Manconi B, Messana I, Castagnola M, Faa G.

Divisione di Anatomia Patologica, Dipartimento di Citomorfologia, University of Cagliari, Cagliari, Italy. Abstract BACKGROUND: Thymosin beta 4 (Tbeta(4)) is a member of beta-thymosins, a family of peptides that play essential roles in many cellular functions. A recent study from our group suggested a role for Tbeta(4) in the development of human salivary glands. The aim of this study was to analyze the expression of Tbeta(4) in the human gut during development, and in the adult.

METHODOLOGY/PRINCIPAL FINDINGS: Immunolocalization of Tbeta(4) was studied in autoptic samples of tongue, oesophagus, stomach, ileum, colon, liver and pancreas obtained from two human foetuses and two adults. Tbeta(4) appeared unevenly distributed, with marked differences between foetuses and adults. In the stomach, superficial epithelium was positive in foetuses and negative in adults. Ileal enterocytes were strongly positive in the adult and weakly positive in the foetuses. An increase in reactivity for Tbeta(4) was observed in superficial colon epithelium of adults as compared with the foetuses. Striking differences were found between foetal and adult liver: the former showed a very low reactivity for Tbeta(4) while in the adult we observed a strong reactivity in the vast majority of the hepatocytes. A peculiar pattern was found in the pancreas, with the strongest reactivity observed in foetal and adult islet cells.

SIGNIFICANCE: Our data show a strong expression of Tbeta(4) in the human gut and in endocrine pancreas during development. The observed differential expression of Tbeta(4) suggests specific roles of the peptide in the gut of foetuses and adults. The observed heterogeneity of Tbeta(4) expression in the foetal life, ranging from a very rare detection in liver cells up to a diffuse reactivity in endocrine pancreas, should be taken into account when the role of Tbeta(4) in the development of human embryo is assessed. Future studies are needed to shed light on the link between Tbeta(4) and organogenesis.

PMID: 20161756

TGF-β2 Suppresses Macrophage Cytokine Production and Mucosal Inflammatory Responses in the Developing Intestine

Maheshwari A, Kelly DR, Nicola T, Ambalavanan N, Jain SK, Murphy-Ullrich J, Athar M, Shimamura M, Bhandari V, Aprahamian C, Dimmitt RA, Serra R, Ohls RK. Gastroenterology. 2010 Sep 24. [Epub ahead of print] PMID: 20875417


"Premature neonates born before 32 weeks of gestation or with a birth weight <1500 grams are predisposed to necrotizing enterocolitis (NEC), an idiopathic, inflammatory bowel necrosis characterized by pneumatosis intestinalis (accumulation of gaseous products of bacterial fermentation within the bowel wall)"

"occurrence of NEC only after postnatal bacterial colonization and never in the sterile intrauterine microenvironment prior to birth"

"NEC is believed to occur when mucosal injury or altered permeability in the preterm intestine permits the translocation of luminal bacteria across the epithelial barrier, which, in turn, triggers a severe inflammatory response"


2009

Bioessays. 2009 Oct;31(10):1026-37. Left-right asymmetry in gut development: what happens next? Burn SF, Hill RE. Source MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK. Abstract The gastrointestinal tract is an asymmetrically patterned organ system. The signals which initiate left-right asymmetry in the developing embryo have been extensively studied, but the downstream steps required to confer asymmetric morphogenesis on the gut organ primordia are less well understood. In this paper we outline key findings on the tissue mechanics underlying gut asymmetry, across a range of species, and use these to synthesise a conserved model for asymmetric gut morphogenesis. We also discuss the importance of correct establishment of left-right asymmetry for gut development and the consequences of perturbations in this process.

PMID: 19708022

The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature.

Wilm B, Ipenberg A, Hastie ND, Burch JB, Bader DM.

Most internal organs are situated in a coelomic cavity and are covered by a mesothelium. During heart development, epicardial cells (a mesothelium) move to and over the heart, undergo epithelial-mesenchymal transition (EMT), and subsequently differentiate into endothelial and vascular smooth muscle cells. This is thought to be a unique process in blood vessel formation. Still, structural and developmental similarities between the heart and gut led us to test the hypothesis that a conserved or related mechanism may regulate blood vessel development to the gut, which, similar to the heart, is housed in a coelomic cavity. By using a combination of molecular genetics, vital dye fate mapping, organ culture and immunohistochemistry, we demonstrate that the serosal mesothelium is the major source of vasculogenic cells in developing mouse gut. Our studies show that the gut is initially devoid of a mesothelium but that serosal mesothelial cells expressing the Wilm's tumor protein (Wt1) move to and over the gut. Subsequently, a subset of these cells undergoes EMT and migrates throughout the gut. Using Wt1-Cre genetic lineage marking of serosal cells and their progeny, we demonstrate that these cells differentiate to smooth muscle of all major blood vessels in the mesenteries and gut. Our data reveal a conserved mechanism in blood vessel formation to coelomic organs, and have major implications for our understanding of vertebrate organogenesis and vascular deficiencies of the gut.

PMID: 16284122


Pancreas cell fate

http://www.ncbi.nlm.nih.gov/pubmed/19750517

"Diabetes is characterized by decreased function of insulin-producing beta cells and insufficient insulin output resulting from an absolute (Type 1) or relative (Type 2) inadequate functional beta cell mass. Both forms of the disease would greatly benefit from treatment strategies that could enhance beta cell regeneration and/or function. Successful and reliable methods of generating beta cells or whole islets from progenitor cells in vivo or in vitro could lead to restoration of beta cell mass in individuals with Type 1 diabetes and enhanced beta cell compensation in Type 2 patients. A thorough understanding of the normal developmental processes that occur during pancreatic organogenesis, for example, transcription factors, cell signaling molecules, and cell-cell interactions that regulate endocrine differentiation from the embryonic pancreatic epithelium, is required in order to successfully reach these goals. This review summarizes our current understanding of pancreas development, with particular emphasis on factors intrinsic or extrinsic to the pancreatic epithelium that are involved in regulating the development and differentiation of the various pancreatic cell types. We also discuss the recent progress in generating insulin-producing cells from progenitor sources."


<pubmed>6502578</pubmed> <pubmed>18075226</pubmed>


Self Assessment Questions

  1. What is a pharyngeal arch and pouch? List the muscle, arch cartilage and nerves of each arch. List the derivatives of each pharyngeal pouch.
  2. Describe the main steps in the development of the tongue.
  3. What are the derivatives of the fore-, mid- and hind-gut?
  4. What is the buccopharyngeal membrane?
  5. How does the thyroid gland develop?
  6. Describe the normal development of the face and palate. List the major malformations of this region and their possible causes.
  7. How is the liver developed?
  8. What are the main processes involved in the elongation and rotation of the stomach and intestinal region?
  9. Describe the development of the pancreas.
  10. How does the myenteric plexus develop?
  11. List the basic principles in the development of the peritoneum.
  12. What are the functions of the liver and pancreas in the fetus? Does the gastro-intestinal tract function in the fetus?
  13. What are the consequences of malrotation of the gut?