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1. Author(s): Matthew Velkey, 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution â Non-Commercial â Share Alike 3.0 License : http://creativecommons.org/licenses/by-nc-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact [email_address] with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised : Some medical content is graphic and may not be suitable for all viewers.
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7. Gastrulation: Epiblast cells migrate through the primitive streak. Definitive (embryonic) endoderm cells displace the hypoblast. Mesoderm spreads between endoderm and ectoderm. Langmanâs Medical Embryology, 9 th ed. 2004.
8. Early mesodermal patterning: (buccopharyngeal membrane) Specific regions of the epiblast migrate through the streak at different levels and assume different positions within the embryo: Source Undetermined Cranial to caudal: Notochord (n) Paraxial mesoderm (pm) Intermediate mesoderm (im) * Lateral plate mesoderm (lpm) Extraembryonic mesoderm (eem)
9. The developing endoderm (yellow) is initially open to the yolk sac (the cardiac region is initially most anterior)⊠Longitudinal folding at both ends of the embryo and lateral folding at the sides of the embryo bring the endoderm inside and form the gut tube. Endoderm Langmanâs Medical Embryology, 9th ed. 2004.
10. Folding creates the anterior and posterior intestinal portals (foregut and hindgut, respectively) The cardiac region is brought to the ventral side of the developing gut tube. Cloacal membrane Langmanâs Medical Embryology, 9th ed. 2004. Juxtaposition of ectoderm and endoderm at: Oropharyngeal (buccopharyngeal) membrane - future mouth Cloacal membrane - future anus
11. Gut-associated organs begin to form as buds from the endoderm: (e.g., thyroid, lung, liver, pancreas) Midgut opening to the yolk sac progressively narrows Langmanâs Medical Embryology, 9th ed. 2004.
12. By the end of the first month: The stomach bulge is visible, Dorsal pancreas has begun to bud Connection of the midgut to the yolk sac is reduced to a yolk stalk Langmanâs Medical Embryology, 9th ed. 2004.
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14. Foregut: pharynx thyroid esophagus parathyroid glands stomach tympanic cavity proximal duodenum trachea, bronchi, lungs liver, gallbladder pancreas Midgut: proximal duodenum to right half of transverse colon Hindgut: left half of urinary bladder transverse colon to anus Gut tube proper Derivatives of gut tube (These three regions are defined by their blood supply)
15. 25 days 32 days Celiac artery supplies the foregut Superior mesenteric artery supplies the midgut Inferior mesenteric artery supplies the hindgut Langmanâs Medical Embryology, 9 th ed. 2004.
16. Gut = bilayered tube (endoderm surrounded by mesoderm) Regional gut tube patterning and organogenesis require bi-directional endoderm-mesoderm cross-talk and inductive signals from other nearby structures Regional patterning of the gut tube Source Undetermined
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19. Hedgehog signaling is important for concentric (radial) patterning of the entire gut tube Morphogen: induces different cell fates at different concentrations of signal Source Undetermined Wheaterâs Functional Histology M. Velkey. Hh Fetus High Hedgehog concentration inhibits muscle formation; Sm. Musc. Sm. Musc Low Hedgehog concentration stimulates muscle differentiation Adult Esophagus
20. Esophageal/Gastric border Esophagus Stomach Cranial-caudal pattern of the gut tube is played out as regional organ differentiation. Distinct borders form. Source Undetermined
27. Once specified, the hepatoblasts proliferate and invade the septum transversum Angioblasts (endothelial cell precursors) are found next to the thickening pre-hepatic endoderm before invasion of the liver bud; these endothelial cells supply critical growth signals Three signals for liver formation: FGF from cardiac mesenchyme; BMPs from septum transversum mesenchyme, VEGF from endothelial cells (anlage formation) Source Undetermined
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31. Defects associated with gut herniation and rotation: oomphaocoele Langmanâs Medical Embryology, 9 th ed. 2004.
32. Defects associated with gut herniation and rotation: vitelline duct abnormalities Langmanâs Medical Embryology, 9 th ed. 2004.
33. Defects associated with gut herniation and rotation: abnormal rotation Absent or incomplete secondary rotation Reversed primary rotation (90° CW) Langmanâs Medical Embryology, 10 th ed. 2006.
34. Defects associated with gut herniation and rotation: volvulus Fixation of a portion of the gut tube to the body wall; subsequent rotation causes twisting of the tube, possibly resulting in stenosis and/or ischemia. Original Image: Carlson - Human Embryology and Developmental Biology, 4th Edition. Image of defects with gut herniation and rotation removed.
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Editor's Notes
Fig 13.3
Fig 13.14
Shh is expressed throughout the endoderm beginning at the time of portal formation Sonic in the endoderm is responsible for inducing other genes in the mesoderm. For example, Shh induces BMP4 in the mesoderm. But this induction is regional and does not occur in the stomach. BMP inhibits proliferation of muscle; ectopic expression of BMP4 in the stomach mesoderm makes the stomach muscle look like intestinal muscle, much less robust. Therefore, the restriction of BMP4 expression from the stomach seems to be important for stomach muscle formation. But this is temporally restricted, because very early on, BMP4 IS expressed in the stomach and this is required for pyloric sphincter formation. Shh also induces the expression of Hox genes in the mesoderm. For example, it induces Hoxd13 in the hindgut, but not the midgut. However, ectopic expression of Hoxd13 in the midgut makes the endoderm develop like hindgut. It is not clear why only hindgut mesoderm is competent to express hoxd13 in response to the Shh signal.
In the gut, the Hh signal also plays a key patterning role. Both Shh and Ihh are expressed early in the endodermal tube of the developing intestine, forming a concentration gradient. Here the Hh signal is critical for radial patterning of mesenchymal structures of the gut. Mostly from studies in the developing Chick, it was shown that Shh induces Bmp4 in adjacent mesenchyme, which then controls growth of stroma and smooth muscle. Shh is also critical for establishment of smooth muscle and neuronal populations, but only in the outer regions of the gut tube. This patterning effect is due to the inhibition of these structures at higher concentrations of Shh, closer to the endodermal tube. Later in development, after villus formation, Shh and Ihh expression becomes confined to the intervillus region of the epithelium, and subsequent epithelial crypt compartment. The role of the Hh signal in this location during late intesintal development is currently unknown.
Endothelial cells also are required for pancreas formation and in the development of the glandular stomach and lung. It is not known where these cells come from, are they recruited, or are they converted form local mesencymal precursors. The liver spends most of its fetal life being a site for hematopoiesis, so the relationship between vascular and hematopoietic development and liver development is a continuing one.