The role of transcription factors in the differentiation of sensory interneurons in the embryo and from hiPSCs.

• Grant number: 23/12306-9
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Chao Yun Irene Yan
• Grantee: Chao Yun Irene Yan
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The spinal cord links the central nervous system to non-neural target tissues. To perform its function, it relies on a wide variety of interneurons. Of these, those in the dorsal region receive, modulate and transmit sensory information. The embryogenesis of medullary neuronal identities is gradual and depends on the combinatorial partnership between several transcription factors.The general objective of the project is to identify the action of transcription factors expressed in the intermediate zone of the neural tube and to map genetic interactions in the differentiation of dorsal interneurons during embryogenesis and iPSCs differentiation.The transcription factors NEUROD4 and SCRT2 have restricted expression in the intermediate zone the neural tube. SCRT2 is a transcription factor that acts as a repressor, while NEUROD4 is a transcriptional regulator that cooperates with other factors in motor neuron differentiation. Both are expressed in sensory interneurons but have different effects on target gene expression. Here we propose to detail the genomic regulatory regions recognized by SCRT2 and NEUROD4. Furthermore, we will follow the evolution of molecular markers of induced pluripotent stem cells (iPSCs) during their differentiation into dorsal spinal cord interneurons. This characterization aims to optimize iPSCs differentiation protocols after comparison with embryonic differentiation. (AU)