Transcription factors in the development of the central and peripheral nervous systems

• Grant number: 20/07008-0
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2021
• End date: September 30, 2023
• 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 neural differentiation of the central and peripheral nervous system depends on the evolution of the transcriptome. Transcriptomic changes in neural differentiation depend on the pattern of expression of several factors. Considering the diversity of cell types generated in the nervous system, the number of neural transcription factors is limited. In other words, complexity in the transcriptomic outcome depends on the combinatorial biochemical and genetic interaction between transcription factors Therefore, the panel of transcription factors expressed concurrently determines the spectrum of differentiation pathways available. The complexity of these interactions is typically mapped into a gene regulatory network (Gene Regulatory Network). These networks include information about the target genes of transcription factors and the back-regulation relationships.SCRATCH2 is a Zn-type transcription factor that modulates the activity of bHLH transcription factors. Its presence in restricted populations of the central and peripheral nervous system indicates that it is an important component of the process of restricting differentiation pathways during the development of the nervous system. Our preliminary data and analyzes suggested that the BARHL1 and LHX9 transcription factors are SCRATCH2 targets in dorsal medullary interneuron precursors. In the peripheral nervous system, ISL1, SOX11, NEUROG1 / 2 and POU4F1 are candidates for SCRATCH2 target genes. Taken together, these possibilities specify the position of SCRATCH2 in the gene regulatory network of two neural structures. Here, we propose to functionally validate the role of SCRATCH2 and map the connectome of other transcription factors co-expressed with SCRATCH2 in the development of the posterior neural tube / spinal cord and in the development of GRD. (AU)