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Pedgihep

Pediatric Gastroenterology, Hepatology & Nutrition

PRECLINICS IN GASTROINTESTINAL EMBRYOLOGY

Genes:homeotic genes :hox a, b,c,d genes :They encode transcription factors for homeobox sequence which regulate segmentation and pattern formation. Disturbances in developement of hox genes lead to organ specific defects in gi tract.for e.g hox c -4 abnormalitycan give rise to esophageal obstruction,hoxd 12 and d13 defect in anal musculature.Hox genes are critical reguators of organ differentiation , patterning and proximal to distal progression.BMP4:Stomach mesoderm,sidedeness of stomach,location of pyloric sphincter while shh signaling induces formation of lamina propria and submucosa .

Esophagus:4 weeks as tubular structure.10 weeks with ciliated columnar epithelium,stratification begins mid -esophagus and progress up and down from 20 weeks.circular muscle is present at 8 weeks,longitudinal muscle at 13 weeks.Nks2.1 separates esophagus from trachea.Basal cells in epithelium have stem cells properties.

Stomach:basic structure is well formed at 14 weeks. Recently Polymerism of nitric oxide synthatase has been held  responsible for pyloric stenosis.Wnt and Hedgehog signaling regulates stomach developement.Wnt signaling inhibition is responsible for stomach specific epithelium.COUP-TF11is responsible for side and patterning of developing stomach.Neck region in gastric pits have stem cells capacity & cells move up and down with proliferation.Musashi1 is responsible for antrum.

Liver : bud at 4th week,foxa 1 and foxa 2 are reuired for liver development in human enterocytes.BMP is required for mesodermal interaction of developing entercytes.hepatoblast are considered to be progeniator for earlier biliary epithelium.biliary ducts from in the ductal plate.reminder of ductal plate regresses.formation of bile duct occurs from hilum to periphery.cauded portion of bud give rise to extrahepatic biliry tree and gallbladder.bile comes in duodenum by 4th month.HNF1b delinates intrahepatic bile ducts.

Pancreas:duts formation starts by 30 days.2 ducts fuse by 7 weeks.by 20 weeks enzyme activity is detectable .enzyme secretion begins around 5th month.pdx-1 gene :early pancreatic developement.hlx-9 is involved in dorsal prepancreatic endoderm.ngn3 helps in endocrine path developement.p48 for exocrine developement.

Small intestine:by 13 weeks organogenesis is complete .its faster as compared to rats.mucosal remodelling and villous structure formation progress in cephalocaudal direction begining at 9 weeks.at 10 weeks intervillous epithelium is stratified while apices are columnar.musculoris mucosa by 17 weeks.little information is available on intestinal vascularisation.paneth cells are present by 12 weeks.they provide innate immunity to intestine.Mcells are present by 17 weeks.tufts cells by16 weeks.proliferative cells are restricted to crypts early in developement.Wnt is responsible for cellular proliferation.BMP4 and BMP-2 are involved in intestinal developement synthesised by mesechymal cells .Wnt and BMP signaling are integrated by PI3 and Akt kinases to maintain stem cell compartment in intestine.notch 1 is responsible for proliferating cells.Math1 is responsible for scretory cell lineage.Gfi1,hes1 and ngn3 is responsible for enteroendocrine developement.smal intestinal stem cell domain is still unexplored.

Colon:early primitive stratified epithelium gets converted to vill-crypt by 12 weeks.glycogen content in colonocytes reduces with advancing trimester and it reappears with carcinoma progression.

 

REVIEWED Refrences:

Neu: Gastroenterology and Nutrition - Neonatology Questions and Controversies, 1st ed

Boulet AM, Capecchi MR: Targeted disruption of hoxc-4 causes esophageal defects and vertebral transformations.  Dev Biol  1996; 177:232-249.

Pollock RA, Jay G, Bieberich CJ: Altering the boundaries of hox3.1 expression: Evidence for antipodal gene regulation.  Cell  1992; 71:911-923.

Smith DM, Tabin CJ: Bmp signalling specifies the pyloric sphincter.  Nature  1999; 402:748-749

Theodosiou NA, Tabin CJ: Sox9 and nkx2.5 determine the pyloric sphincter epithelium under the control of bmp signaling.  Dev Biol  2005; 279:481-490

Minoo P, Su G, Drum H, et al: Defects in tracheoesophageal and lung morphogenesis innkx2.1(-/-) mouse embryos.  Dev Biol  1999; 209:60-71.

Vanderwinden J, Mailleux P, Schiffmann S, et al: Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis.  N Engl J Med  1992; 327:511-515

Takamoto N, You L-R, Moses K, et al: Coup-tfii is essential for radial and anteroposterior patterning of the stomach.  Development  2005; 132:2179-2189

Lee CS, Friedman JR, Fulmer JT, Kaestner KH: The initiation of liver development is dependent on foxa transcription factors.  Nature  2005; 435:944-947

 McClean P, Weaver LT: Ontogeny of human pancreatic exocrine function.  Arch Dis Child  1993; 68:62-65.

 Edlund H: Pancreatic organogenesis – developmental mechanisms and implications for therapy.  Nat Rev Genet  2002; 3:524-532

Bevins CL: Events at the host-microbial interface of the gastrointestinal tract v. Paneth cell {alpha}-defensins in intestinal host defense.  Am J Physiol Gastrointest Liver Physiol  2005; 289:G173-G176.

Booth C, Potten CS: Gut instincts: Thoughts on intestinal epithelial stem cells.  J Clin Invest  2000; 105:1493-1499

Logan CY, Nusse R: The wnt signaling pathway in development and disease.  Annu Rev Cell Dev Biol  2004; 20:781-810

 Jensen J, Pedersen EE, Galante P, et al: Control of endodermal endocrine development by hes-1.  Nat Genet  2000; 24:36-44.

Shaoul R, Hong D, Okada Y, et al: Lineage development in a patient without goblet, paneth, and enteroendocrine cells: A clue for intestinal epithelial differentiation.  Pediatr Res  2005; 58:492-498

 Schonhoff SE, Giel-Moloney M, Leiter AB: Neurogenin 3-expressing progenitor cells in the gastrointestinal tract differentiate into both endocrine and non-endocrine cell types.  Dev Biol  2004; 270:443-454

Rousset M, Robine-Leon S, Dussaulx E, et al: Glycogen storage in foetal and malignant epithelial cells of the human colon.  Front Gastrointest Res  1979; 4:80-85

 Oyama Y, Craig RM, Traynor AE, et al: Autologous hematopoietic stem cell transplantation in patients with refractory crohn's disease.  Gastroenterology  2005; 128:552-563

Bondurand N, Natarajan D, Thapar N, et al: Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures.  Development  2003; 130:6387-6400.

pre and paraclinical sciences.

PEDGIHEP is actively working on pre and paraclinical sciences related to pediatric gastrointestinal hepatology.

Editorial borad is working  on guidelines, meta-analysis and reviews on various topics.

CURRENT REVIEW:Editorial board of pediatric gastrointestinal ana-radiological sciences is  at present working on standard morphology of gastro-liver organs :weight, length and correlating  their morphology with age and sex in children.

if interested in knowing further details :can mail: pedgihep@yahoo.com

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