Presentation Title

Investigations into Prickle, a direct target of miR361

Start Date

November 2016

End Date

November 2016

Location

MSE 103

Type of Presentation

Oral Talk

Abstract

Many human birth defects entail malformations in the craniofacial skeleton or the long bones while others are associated with altered bone mineral density. During embryonic development, bone cells may be specified from various progenitors via multiple mechanisms either involving cartilage precursors or not. Multiple decades of studying the molecular underpinnings of bone development, often focused on the analyses of specific DNA-binding transcription factors, has resulted in a general understanding of this complex process. This knowledge has helped genetic counselors assess the likelihood of developing skeletal defects in at-risk populations. Still, many skeletal birth defects remain incompletely understood. Importantly, the role of microRNAs (miRNAs), a novel class of epigenetic modifiers, in how bone cells are specified has not been thoroughly analyzed, and could provide new avenues to diagnose and prevent skeletal malformations.

Using mouse and human pluripotent stem cells, we previously identified a miRNA that potently enhances osteogenic differentiation in vitro: miR361 and that binds to the 3’ untranslated region of Prickle. Since PRICKLE has been reported as a nuclear translocator for the transcriptional repressor REST, we hypothesized that miR361 promotes osteogenesis by preventing REST nuclear localization lifting its repression. Here, we confirm that the nuclear absence of REST upon miR361 overexpression correlated with the enhanced expression of differentiation markers. We further initiated investigations into the specific isoform of Prickle involved in this process. Using immunocytochemistry, we provide first evidence for a potential role for PRICKLE1 in the regulation of REST.

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Nov 12th, 11:00 AM Nov 12th, 11:15 AM

Investigations into Prickle, a direct target of miR361

MSE 103

Many human birth defects entail malformations in the craniofacial skeleton or the long bones while others are associated with altered bone mineral density. During embryonic development, bone cells may be specified from various progenitors via multiple mechanisms either involving cartilage precursors or not. Multiple decades of studying the molecular underpinnings of bone development, often focused on the analyses of specific DNA-binding transcription factors, has resulted in a general understanding of this complex process. This knowledge has helped genetic counselors assess the likelihood of developing skeletal defects in at-risk populations. Still, many skeletal birth defects remain incompletely understood. Importantly, the role of microRNAs (miRNAs), a novel class of epigenetic modifiers, in how bone cells are specified has not been thoroughly analyzed, and could provide new avenues to diagnose and prevent skeletal malformations.

Using mouse and human pluripotent stem cells, we previously identified a miRNA that potently enhances osteogenic differentiation in vitro: miR361 and that binds to the 3’ untranslated region of Prickle. Since PRICKLE has been reported as a nuclear translocator for the transcriptional repressor REST, we hypothesized that miR361 promotes osteogenesis by preventing REST nuclear localization lifting its repression. Here, we confirm that the nuclear absence of REST upon miR361 overexpression correlated with the enhanced expression of differentiation markers. We further initiated investigations into the specific isoform of Prickle involved in this process. Using immunocytochemistry, we provide first evidence for a potential role for PRICKLE1 in the regulation of REST.