Year-end Sale % OFF 
Abstract
Sonic Hedgehog (SHH) and WNT proteins are key regulators in many developmental processes, like embryonic patterning and brain development. In the brain, SHH is expressed in a gradient starting in the floor plate (FP) progressing ventrally in the midbrain, where it is thought to be involved in the development and specification of mesodiencephalic dopaminergic (mdDA) neurons. GLI2A-mediated SHH-signaling induces the expression of Gli1, which is inhibited when cells start expressing SHH themselves. To determine whether mdDA neurons receive GLI2A-mediated SHH-signaling during differentiation, we used a BAC-transgenic mouse model expressing eGFP under the control of the Gli1 promoter. This mouse-model allowed for mapping of GLI2A-mediated SHH-signaling temporal and spatial in the mouse midbrain. Since mdDA neurons are born from E10.5, peaking at E11.0–E12.0, we examined Gli1-eGFP embryos at E11.5, E12.5, and E13.5, indicating whether Gli1 was induced before or during mdDA development and differentiation. Our data indicate that GLI2A-mediated SHH-signaling is not involved in mdDA neuronal differentiation. However, it appears to be involved in the differentiation of neurons which make up a subset of the red nucleus (RN). In order to detect whether mdDA neuronal differentiation may be under the control of canonical WNT-signaling, we used a transgenic mouse-line expressing LacZ under the influence of stable β-catenin. Here, we show that TH+ neurons of the midbrain receive canonical WNT-signaling during differentiation. Therefore, we suggest that early SHH-signaling is indirectly involved in mdDA development through early patterning of the midbrain area, whereas canonical WNT-signaling is directly involved in the differentiation of the mdDA neuronal population.
Highlights
The mesodiencephalic dopaminergic group of neurons consists of different neuronal subsets, each dependent on a unique transcriptional code for their development [1,2,3]
We suggest that Sonic Hedgehog (SHH)-signaling is indirectly involved in mesodiencephalic dopaminergic (mdDA) neuronal differentiation through early patterning of the floor plate (FP) and midbrain area, whereas canonical WNT-signaling is directly involved in differentiation of the mdDA neuronal population
Much is known about the development of the mesodiencephalic dopaminergic system at late stages, the question remains how these neurons differentiate in early stages and where mdDA neurons originate
Summary
The mesodiencephalic dopaminergic (mdDA) group of neurons consists of different neuronal subsets, each dependent on a unique transcriptional code for their development [1,2,3]. These subsets are thought to be specified when terminal differentiation progresses [3]. Within the brain SHH is expressed in a gradient starting at the FP, which is required for correct dorsal-ventral (DV) patterning of the neural tube [6,7] This gradient is formed by SHH-N, the active component of SHH created by autoproteolytic cleavage [8,9]. The precise function of GLI1 is not known, but its initial transcription is dependent on GLI2A-mediated SHH-signaling and is abolished when cells start expressing SHH themselves [11,12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
