Year-end Sale % OFF 
Abstract
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively. To refine our understanding of the regional-specific relationships between En1 and Pitx3 and their (combined) role in the programming mdDA neurons on the rostral-to-caudal axis, we created double En1tm1Alj/tm1Alj;Pitx3gfp/gfp (En1KO;Pitx3GFP/GFP) animals. Here we report, that in absence of En1 and Pitx3, only a limited number of mdDA neurons are present at E14.5. These mdDA neurons have a rudimentary dopaminergic cell fate, as they express Nurr1, Pbx3 and Otx2 but have lost their rostral or caudal subset identity. Furthermore, we report that the expression of Cck depends on En1 expression, while (in contrast) both Pitx3 and En1 are involved in the initiation of Ahd2 expression. Thus we reveal in this manuscript that regulated levels of Pitx3 and En1 control the size and rostral/caudal-identity of the mdDA neuronal population.
Highlights
The neurons of the substantia nigra (SNc) and the ventral tegmental area (VTA) originate in from the di- and mesencephalon, and as such are called mesodiencephalic dopaminergic neurons
Our research group previously investigated single Pitx3KO and En1KO animals to better understand the role of Pitx3 and Engrailed 1 (En1) during the development of mesodiencephalic dopaminergic (mdDA) neurons
We showed that in absence of Pitx3 the SNc is absent [31] and in absence of En1 we observed a dramatic loss of Th-expressing cells, that included mdDA neurons from both the SNc and VTA [13]
Summary
The neurons of the substantia nigra (SNc) and the ventral tegmental area (VTA) originate in from the di- and mesencephalon, and as such are called mesodiencephalic dopaminergic (mdDA) neurons. These neurons are important enforcers of movement and motivation, and are targeted in neurodegenerative pathologies, such as Parkinson’s Disease (PD). Pitx and En1 converge in developing dopamine neurons specific vulnerability of mdDA neurons, many efforts have been made to understand the molecular similarities and differences between SNc and VTA neurons. Several studies from our group contributed to the quest to define molecular profiles for different mdDA subsets already during embryonic development [7,8,9,10]. Elegant transcriptomic studies identified these molecular profiles in single-cellular resolution in early post-natal tissue [11], as well as during embryonic development of both murine and human tissue [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.
