Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/30736
Title: Cellular and molecular control of skeleton formation in fish: Insights from osteoblast ablation and functional characterization of Lrp5 and SOst
Authors: BERND WILLEMS
Keywords: developmental biology, genetics, zebrafish, medaka, skeleton, bone
Issue Date: 18-Aug-2011
Source: BERND WILLEMS (2011-08-18). Cellular and molecular control of skeleton formation in fish: Insights from osteoblast ablation and functional characterization of Lrp5 and SOst. ScholarBank@NUS Repository.
Abstract: A structure common to all vertebrate species is their axial skeleton, which is composed of a calcified extracellular matrix deposited by bone forming cells (osteoblasts) We use the two laboratory fish species medaka (Orizyas latipes) and zebrafish (Danio rerio) as models to gain better understanding about cellular and molecular processes involved in skeletal development. To gain a better understanding about the role of osteoblasts in development of the vertebral column, we created a transgenic osx:CFP-NTR medaka which enables conditional ablation of this cell lineage upon antibiotic treatment. Absence of the majority of osteoblasts, which was evident by reduced reporter expression, enhanced apoptosis in the respective regions and reduced marker gene expression lead to reduced bone mass in the cranial skeleton and the vertebral spines. In contrast, vertebral bodies were found partially fused as a result of osteoblast ablation. Thus, we propose an additional function for these cells as growth restricting border cells in development of the vertebral bodies. In the course of vertebrate development, cranial neural crest cells (CNCCs) undergo an epithelial to mesenchymal transition (EMT), delaminate from the neural plate and migrate in separate mesenchymal streams to invade the respective cranial regions in which they subsequently differentiate to form the craniofacial skeleton. Canonical Wnt pathway is thereby one of the essential signaling cascades. Here we show that the frizzled co-receptor low-density-lipoprotein (LDL) receptor-related protein 5 (Lrp5) plays a crucial role in CNCC development and morphogenesis of the cranial skeleton. Morpholino mediated knockdown of lrp5 does not affect induction of CNCCs. However, it leads to reduced proliferation of premigratory CNCCs. Additionally CNCC migration is disturbed as ectopic cells are found in the dorsal neuroepithelium. These defects eventually result in craniofacial skeleton malformations. Interestingly, knockdown of Sost, a putative inhibitor of Lrp5 leads to similar defects. Both factors have to date mainly been associated with bone metabolism in man and mammals. This is the first report about an involvement in early morphogenetic processes.
URI: http://scholarbank.nus.edu.sg/handle/10635/30736
Appears in Collections:Ph.D Theses (Open)

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