Proper BMP Signaling Levels Are Essential for 3D Assembly of Hepatic Cords from Hepatoblasts and Mesenchymal Cells

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2015 Jul 16

PMID 26173507

Citations 1

Authors

Ming-Shian Tsai

Sanong Suksaweang

Ting-Xin Jiang

Ping Wu

Ying-Hsien Kao

Po-Huang Lee

Randall Widelitz

Cheng-Ming Chuong

Affiliations

Soon will be listed here.

Abstract

Background: Because the molecular mechanisms of morphogenesis of the hepatic cord and sinus are unclear, we investigated the involvement of bone morphogenetic protein (BMP4) in hepatic sinusoid morphogenesis.

Methods: We used embryonic chicken livers, which develop rapidly, as our model, and investigated expression of BMP-related genes. BMP4 activity was manipulated by overexpressing BMP4 and its antagonist, noggin.

Results: During hepatic cord morphogenesis, BMP4 and its receptors are expressed in both peri-sinusoidal cells and hepatoblasts as the sinusoids form, whereas noggin is expressed transiently in peri-sinusoidal cells at early stages. Suppression of BMP activity with noggin overexpression disrupted normal hepatic sinusoid structure, leading to liver congestion, failure of fibronectin deposition, and markedly reduced numbers of peri-sinusoidal cells. However, overexpression of BMP did not change sinusoidal morphology but increased endothelial cell number. Noggin overexpression resulted in disrupted cord organization, and dilated sinusoidal space, eventually leading to increased apoptosis and failed hepatocyte differentiation.

Conclusions: Our results show that proper BMP signaling mediates peri-sinusoidal cell-hepatoblast interactions during development; this is essential for hepatic cord organization among hepatoblasts, endothelium, and presumptive hepatic stellate cells.

Citing Articles

Generation of Hepatocytes and Nonparenchymal Cell Codifferentiation System from Human-Induced Pluripotent Stem Cells.

Shi Y, Deng J, Sang X, Wang Y, He F, Chen X Stem Cells Int. 2022; 2022:3222427.

PMID: 36467281 PMC: 9709383. DOI: 10.1155/2022/3222427.

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