The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation

Stem Cell Reports
Daniel GyllborgErnest Arenas

Abstract

The development of midbrain dopaminergic (mDA) neurons is controlled by multiple morphogens and transcription factors. However, little is known about the role of extracellular matrix proteins in this process. Here we examined the function of roof plate-specific spondins (RSPO1-4) and the floor plate-specific, spondin 1 (SPON1). Only RSPO2 and SPON1 were expressed at high levels during mDA neurogenesis, and the receptor LGR5 was expressed by midbrain floor plate progenitors. Surprisingly, RSPO2, but not SPON1, specifically promoted the differentiation of mDA neuroblasts into mDA neurons in mouse primary cultures and embryonic stem cells (ESCs). In addition, RSPO2 was found to promote not only mDA differentiation, but also mDA neurogenesis in human ESCs. Our results thus uncover an unexpected function of the matricellular protein RSPO2 and suggest an application to improve mDA neurogenesis and differentiation in human stem cell preparations destined to cell replacement therapy or drug discovery for Parkinson disease.

Citations

Jul 10, 2019·Molecular & Cellular Proteomics : MCP·Filip HumenikMichel Salzet
Jul 8, 2020·International Journal of Molecular Sciences·Simone Mesman, Marten P Smidt
Sep 10, 2020·Frontiers in Cell and Developmental Biology·Tae Wan KimLorenz Studer
Sep 1, 2019·Molecular & Cellular Proteomics : MCP·Filip HumenikMichel Salzet
Apr 4, 2021·International Journal of Molecular Sciences·Seon-Ung HwangSang-Hwan Hyun

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BETA
ubiquitination
RNA-seq
PCR

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