Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum
GABAergic inhibitory neurons in the cerebellum are subdivided into Purkinje cells and distinct subtypes of interneurons from the same pool of progenitors, but the determinants of this diversification process are not well defined. To explore the transcriptional regulation of the development of cerebe...
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doaj-c9697933b70442628b599b83f6a5e7702020-11-24T23:23:12ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-08-011010.3389/fnmol.2017.00281283462Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing CerebellumNorliyana Zainolabidin0Norliyana Zainolabidin1Sandhya P. Kamath2Sandhya P. Kamath3Ayesha R. Thanawalla4Ayesha R. Thanawalla5Albert I. Chen6Albert I. Chen7Albert I. Chen8School of Biological Sciences, Nanyang Technological University (NTU)Singapore, SingaporeSchool of Life Sciences, University of WarwickCoventry, United KingdomSchool of Biological Sciences, Nanyang Technological University (NTU)Singapore, SingaporeSchool of Life Sciences, University of WarwickCoventry, United KingdomSchool of Biological Sciences, Nanyang Technological University (NTU)Singapore, SingaporeSchool of Life Sciences, University of WarwickCoventry, United KingdomSchool of Biological Sciences, Nanyang Technological University (NTU)Singapore, SingaporeSchool of Life Sciences, University of WarwickCoventry, United KingdomA*STAR, Institute of Molecular and Cell BiologySingapore, SingaporeGABAergic inhibitory neurons in the cerebellum are subdivided into Purkinje cells and distinct subtypes of interneurons from the same pool of progenitors, but the determinants of this diversification process are not well defined. To explore the transcriptional regulation of the development of cerebellar inhibitory neurons, we examined the role of Tfap2A and Tfap2B in the specification of GABAergic neuronal subtypes in mice. We show that Tfap2A and Tfap2B are expressed in inhibitory precursors during embryonic development and that their expression persists into adulthood. The onset of their expression follows Ptf1a and Olig2, key determinants of GABAergic neuronal fate in the cerebellum; and, their expression precedes Pax2, an interneuron-specific factor. Tfap2A is expressed by all GABAergic neurons, whereas Tfap2B is selectively expressed by interneurons. Genetic manipulation via in utero electroporation (IUE) reveals that Tfap2B is necessary for interneuron specification and is capable of suppressing the generation of excitatory cells. Tfap2A, but not Tfap2B, is capable of inducing the generation of interneurons when misexpressed in the ventricular neuroepithelium. Together, our results demonstrate that the differential expression of Tfap2A and Tfap2B defines subtypes of GABAergic neurons and plays specific, but complementary roles in the specification of interneurons in the developing cerebellum.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00281/fullTfap2ATfap2BcerebellumGABAergic interneuronstranscription factorsdevelopment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Norliyana Zainolabidin Norliyana Zainolabidin Sandhya P. Kamath Sandhya P. Kamath Ayesha R. Thanawalla Ayesha R. Thanawalla Albert I. Chen Albert I. Chen Albert I. Chen |
spellingShingle |
Norliyana Zainolabidin Norliyana Zainolabidin Sandhya P. Kamath Sandhya P. Kamath Ayesha R. Thanawalla Ayesha R. Thanawalla Albert I. Chen Albert I. Chen Albert I. Chen Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum Frontiers in Molecular Neuroscience Tfap2A Tfap2B cerebellum GABAergic interneurons transcription factors development |
author_facet |
Norliyana Zainolabidin Norliyana Zainolabidin Sandhya P. Kamath Sandhya P. Kamath Ayesha R. Thanawalla Ayesha R. Thanawalla Albert I. Chen Albert I. Chen Albert I. Chen |
author_sort |
Norliyana Zainolabidin |
title |
Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum |
title_short |
Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum |
title_full |
Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum |
title_fullStr |
Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum |
title_full_unstemmed |
Distinct Activities of Tfap2A and Tfap2B in the Specification of GABAergic Interneurons in the Developing Cerebellum |
title_sort |
distinct activities of tfap2a and tfap2b in the specification of gabaergic interneurons in the developing cerebellum |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2017-08-01 |
description |
GABAergic inhibitory neurons in the cerebellum are subdivided into Purkinje cells and distinct subtypes of interneurons from the same pool of progenitors, but the determinants of this diversification process are not well defined. To explore the transcriptional regulation of the development of cerebellar inhibitory neurons, we examined the role of Tfap2A and Tfap2B in the specification of GABAergic neuronal subtypes in mice. We show that Tfap2A and Tfap2B are expressed in inhibitory precursors during embryonic development and that their expression persists into adulthood. The onset of their expression follows Ptf1a and Olig2, key determinants of GABAergic neuronal fate in the cerebellum; and, their expression precedes Pax2, an interneuron-specific factor. Tfap2A is expressed by all GABAergic neurons, whereas Tfap2B is selectively expressed by interneurons. Genetic manipulation via in utero electroporation (IUE) reveals that Tfap2B is necessary for interneuron specification and is capable of suppressing the generation of excitatory cells. Tfap2A, but not Tfap2B, is capable of inducing the generation of interneurons when misexpressed in the ventricular neuroepithelium. Together, our results demonstrate that the differential expression of Tfap2A and Tfap2B defines subtypes of GABAergic neurons and plays specific, but complementary roles in the specification of interneurons in the developing cerebellum. |
topic |
Tfap2A Tfap2B cerebellum GABAergic interneurons transcription factors development |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00281/full |
work_keys_str_mv |
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