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. 2023 Jan 28;24(3):2523. doi: 10.3390/ijms24032523

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© 2023 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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A plethora of small signaling molecules involved in 3 stages of mDA neurodevelopmental fate. The 3 stages are: 1. specification of midbrain floorplate; 2. specification of midbrain DA (mDA) neurons/mDA neurogenesis and suppression of alternative fate; and 3. mDA maturation and survival. The key pathways for specification of ventral midbrain fate are the Wnt1-Otx2-LMX1A-Msx1 pathway (black) and the Shh-FoxA2 pathway (green) that converged to Mash1 and Ngn2 (orange). Small molecules used in in vitro cultures mainly target the inhibition of SMAD signaling that drives epidermal fate and the activation of Wnt and Shh signaling.