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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
IGF-2/IGF-1R signaling has distinct effects on Sox1, Irx3, and Six3 expressions during ES cell derived-neuroectoderm
Nozomu Takata1,2, Eriko Sakakura3, Yoshiki Sasai4
1Laboratory for In Vitro Histogenesis, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuou-ku, Kobe, Hyogo, 650-0047, Japan. nozomutakata@cdb.riken.jp.
Abstract:
Insulin-like growth factors (IGFs) are involved in growth and tissue development, including diseases such as type-2 diabetes and cancers. However, their roles in lineage specification, especially in early mammalian neural development, are poorly understood. Here, we analyzed the protein expression of IGF-2 in early mouse embryo, and it was preferentially detected in anterior mesodermal tissue, adjacent to the neural plate. We utilized a self-organizing neural tissue culture system and analyzed the direct effect of IGF-2 on the general neural marker Sox1. Interestingly, using recombinant IGF-2 and a chemical inhibitor of its receptor (IGF-1R), we found that the IGF-2/IGF-1R pathway positively regulated Sox1 expression in embryonic stem (ES) cell-derived neural tissue. Furthermore, to visualize the expression patterns of other neural markers, we used reporter ES cell lines and we found that the IGF-2/IGF-1R signaling upregulated the expression of the posterior neural marker Irx3. In contrast, the anterior neural marker Six3 was downregulated by IGF-2/IGF-1R signaling. Together, our results demonstrate that IGF-2/IGF-1R signaling has different effects on neural marker expression, which may influence the early regional identity of ES cell-derived neural tissues.
Insights
Insulin-like growth factor-2 (IGF-2) signaling positively regulates neural development markers in early mouse embryos. This pathway influences neural tissue regional identity by differentially affecting anterior and posterior neural markers.
Area of Science:
- Developmental Biology
- Neuroscience
- Molecular Biology
Background:
- Insulin-like growth factors (IGFs) are crucial for growth and tissue development, implicated in diseases like type-2 diabetes and cancer.
- The specific roles of IGFs in early mammalian neural lineage specification remain largely unexplored.
- IGF-2 protein expression is observed in anterior mesodermal tissue adjacent to the neural plate in early mouse embryos.
Purpose of the Study:
- To investigate the function of IGF-2 in early neural development and lineage specification.
- To determine the direct effects of the IGF-2/IGF-1R pathway on neural marker expression in embryonic stem cell-derived neural tissues.
Main Methods:
- Analysis of IGF-2 protein expression in early mouse embryos.
- Utilizing a self-organizing neural tissue culture system derived from embryonic stem (ES) cells.
- Employing recombinant IGF-2 and a chemical inhibitor of its receptor (IGF-1R).
- Assessing the expression of neural markers (Sox1, Irx3, Six3) using reporter ES cell lines.
Main Results:
- The IGF-2/IGF-1R pathway positively regulates the general neural marker Sox1 expression.
- IGF-2/IGF-1R signaling upregulates the posterior neural marker Irx3.
- Conversely, IGF-2/IGF-1R signaling downregulates the anterior neural marker Six3.
Conclusions:
- IGF-2/IGF-1R signaling plays a significant role in early neural development.
- This pathway differentially impacts the expression of anterior and posterior neural markers.
- The findings suggest a mechanism by which IGF-2 influences the regional identity of developing neural tissues.
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