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Left-Right Asymmetrical Liver Develo...

Womble, Mandy Ashton.

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Left-Right Asymmetrical Liver Development.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Left-Right Asymmetrical Liver Development./
Author:	Womble, Mandy Ashton.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
Description:	275 p.
Notes:	Source: Dissertation Abstracts International, Volume: 79-05(E), Section: B.
Contained By:	Dissertation Abstracts International79-05B(E).
Subject:	Developmental biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10708416
ISBN:	9780355459012

Left-Right Asymmetrical Liver Development.
Womble, Mandy Ashton.

Left-Right Asymmetrical Liver Development. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 275 p.

Source: Dissertation Abstracts International, Volume: 79-05(E), Section: B.

Thesis (Ph.D.)--North Carolina State University, 2017.

The liver is one of the many internal organs of the body that is left-right asymmetric in both anatomical location and morphology. In humans, the liver is located on the right side of the body cavity. Additionally, the right side of the liver is larger and consists of more lobes than the left. As many as 1 in 10,000 humans are born with defects in left-right asymmetry that often involve severe anomalies in liver laterality including aberrant lobation, abnormal organ position, and hepatic duct and biliary tree malformations, yet the mechanisms underlying the development of left-right asymmetries in the liver are unknown. In other asymmetric organs like the heart, lungs, stomach, and gastrointestinal tract, leftsided expression of Pitx2c, a homeobox transcription factor, is required for left-right asymmetric organogenesis. In the stomach and gastrointestinal tract of the mouse, chick, and frog, Pitx2c influences cell shape and cell rearrangements. However, it is unknown whether Pitx2c is required for asymmetrical liver development. Using the experimentally amenable embryo of the frog, Xenopus laevis, we show that Pitx2c is necessary and sufficient for leftright asymmetries in cell shape and epithelial character in the liver diverticulum. The right side cells of the liver diverticulum become apically constricted and elongated on the apical to basal axis, as the epithelium expands in surface area and ultimately forms a larger, elongated liver lobe. Pitx2c prevents left side cells from changing shape, inhibiting diverticulum expansion, ultimately resulting in a smaller, rounded liver lobe. This study is one of the first to demonstrate cellular level differences in liver morphogenesis and the first to link these differences to Pitx2c. Interestingly, the cell behaviors we observed downstream of Pitx2c in the liver are different behaviors than those observed in other organ systems demonstrating that Pitx2c's influence on cell behavior and left-right asymmetrical morphogenesis is organ independent and may depend on the geometric constraints of the tissue as well as other factors intrinsic to that organ.

ISBN: 9780355459012Subjects--Topical Terms:

592588
Developmental biology.

Left-Right Asymmetrical Liver Development.
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500 $a Adviser: Nanette Nascone-Yoder.
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520 $a The liver is one of the many internal organs of the body that is left-right asymmetric in both anatomical location and morphology. In humans, the liver is located on the right side of the body cavity. Additionally, the right side of the liver is larger and consists of more lobes than the left. As many as 1 in 10,000 humans are born with defects in left-right asymmetry that often involve severe anomalies in liver laterality including aberrant lobation, abnormal organ position, and hepatic duct and biliary tree malformations, yet the mechanisms underlying the development of left-right asymmetries in the liver are unknown. In other asymmetric organs like the heart, lungs, stomach, and gastrointestinal tract, leftsided expression of Pitx2c, a homeobox transcription factor, is required for left-right asymmetric organogenesis. In the stomach and gastrointestinal tract of the mouse, chick, and frog, Pitx2c influences cell shape and cell rearrangements. However, it is unknown whether Pitx2c is required for asymmetrical liver development. Using the experimentally amenable embryo of the frog, Xenopus laevis, we show that Pitx2c is necessary and sufficient for leftright asymmetries in cell shape and epithelial character in the liver diverticulum. The right side cells of the liver diverticulum become apically constricted and elongated on the apical to basal axis, as the epithelium expands in surface area and ultimately forms a larger, elongated liver lobe. Pitx2c prevents left side cells from changing shape, inhibiting diverticulum expansion, ultimately resulting in a smaller, rounded liver lobe. This study is one of the first to demonstrate cellular level differences in liver morphogenesis and the first to link these differences to Pitx2c. Interestingly, the cell behaviors we observed downstream of Pitx2c in the liver are different behaviors than those observed in other organ systems demonstrating that Pitx2c's influence on cell behavior and left-right asymmetrical morphogenesis is organ independent and may depend on the geometric constraints of the tissue as well as other factors intrinsic to that organ.
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