Neural induction: Historical views and application to pluripotent stem cells

Abstract

Embryonic stem (ES) cells are a useful experimental material to recapitulate the differentiation steps of early embryos, which are usually invisible and inaccessible from outside of the body, especially in mammals. ES cells have greatly facilitated the analyses of gene expression profiles and cell characteristics. In addition, understanding the mechanisms during neural differentiation is important for clinical purposes, such as developing new therapeutic methods or regenerative medicine. As neurons have very limited regenerative ability, neurodegenerative diseases are usually intractable, and patients suffer from the disease throughout their lifetimes. The functional cells generated from ES cells in vitro could replace degenerative areas by transplantation. In this review, we will first demonstrate the historical views and widely accepted concepts regarding the molecular mechanisms of neural induction and positional information to produce the specific types of neurons in model animals. Next, we will describe how these concepts have recently been applied to the research in the establishment of the methodology of neural differentiation from mammalian ES cells. Finally, we will focus on examples of the applications of differentiation systems to clinical purposes. Overall, the discussion will focus on how historical developmental studies are applied to state‐of‐the‐art stem cell research.

Identification of the Time Period during Which BMP Signaling Regulates Proliferation of Neural Progenitor Cells in Zebrafish

“…This process, termed neural induction, specifies the neuroectoderm within the ectoderm and is conserved in vertebrates. However, other signals, such as fibroblast growth factor (FGF) and Wnt, have also been demonstrated as key modulators in neural induction (reviewed in [ 2 ]). These signaling pathways and their downstream transcription factors not only govern neural induction, but also regulate the competence and specification of neural progenitor cells in the neuroectoderm, as well as the formation and expansion of neural plates (reviewed in [ 3 , 4 ]).…”

Regulation of progenitor cell survival by a novel chromatin remodeling factor during neural tube development

“…The neural tube, an embryonic structure of the central nervous system, is a tractable model for analyzing these cellular events. The neural tube has anterior-posterior (A-P) and dorsal-ventral (D-V) polarities, which are controlled by signaling molecules emanating from specific areas called organizers (Sasai et al, 2021). During D-V patterning of the neural tube, progenitor cells in the newly formed neural tube are sensitive to signaling molecules such as bone morphogenetic protein (BMP) and Wnt from the roof plate and Sonic Hedgehog (Shh) from the floor plate and its underlying tissue, the notochord (Le Dreau & Marti, 2012).…”

The Enigmatic Reissner’s Fiber and the Origin of Chordates

“…Nonetheless, the evolutionary origin of chordates themselves remains as one of the great unsolved questions of evolutionary biology ( Satoh, 2008 ; Holland et al, 2015 ). In this context, the notochord is considered by many a cardinal feature of chordates, being involved in the development of some of the principal characters of this phylum, especially the tailbud and the neural tube ( Henrique et al, 2015 ; Sasai et al, 2021 ).…”