» Articles » PMID: 23639443

Prdm13 Mediates the Balance of Inhibitory and Excitatory Neurons in Somatosensory Circuits

Overview
Journal Dev Cell
Publisher Cell Press
Date 2013 May 4
PMID 23639443
Citations 41
Authors
Affiliations
Soon will be listed here.
Abstract

Generating a balanced network of inhibitory and excitatory neurons during development requires precise transcriptional control. In the dorsal spinal cord, Ptf1a, a basic helix-loop-helix (bHLH) transcription activator, maintains this delicate balance by inducing homeodomain (HD) transcription factors such as Pax2 to specify the inhibitory lineage while suppressing HD factors such as Tlx1/3 that specify the excitatory lineage. We uncover the mechanism by which Ptf1a represses excitatory cell fate in the inhibitory lineage. We identify Prdm13 as a direct target of Ptf1a and reveal that Prdm13 actively represses excitatory cell fate by binding to regulatory sequences near the Tlx1 and Tlx3 genes to silence their expression. Prdm13 acts through multiple mechanisms, including interactions with the bHLH factor Ascl1, to repress Ascl1 activation of Tlx3. Thus, Prdm13 is a key component of a highly coordinated transcriptional network that determines the balance of inhibitory versus excitatory neurons in the dorsal spinal cord.

Citing Articles

Revisiting the development of cerebellar inhibitory interneurons in the light of single-cell genetic analyses.

Schilling K Histochem Cell Biol. 2023; 161(1):5-27.

PMID: 37940705 PMC: 10794478. DOI: 10.1007/s00418-023-02251-z.


Climate Adaptation and Drift Shape the Genomes of Two Eel-Goby Sister Species Endemic to Contrasting Latitude.

Lu Z, Liu T, Liu Y, Wang Y, Liu J, Liu B Animals (Basel). 2023; 13(20).

PMID: 37893964 PMC: 10603712. DOI: 10.3390/ani13203240.


Sleep-wake patterns are altered with age, Prdm13 signaling in the DMH, and diet restriction in mice.

Tsuji S, Brace C, Yao R, Tanie Y, Tada H, Rensing N Life Sci Alliance. 2023; 6(6).

PMID: 37045472 PMC: 10105329. DOI: 10.26508/lsa.202301992.


The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.

Al-Kasbi G, Al-Murshedi F, Al-Kindi A, Al-Hashimi N, Al-Thihli K, Al-Saegh A Sci Rep. 2022; 12(1):18862.

PMID: 36344539 PMC: 9640568. DOI: 10.1038/s41598-022-22036-z.


EZH2-Mediated H3K27me3 Targets Transcriptional Circuits of Neuronal Differentiation.

Buontempo S, Laise P, Hughes J, Trattaro S, Das V, Rencurel C Front Neurosci. 2022; 16:814144.

PMID: 35645710 PMC: 9133892. DOI: 10.3389/fnins.2022.814144.


References
1.
Hori K, Cholewa-Waclaw J, Nakada Y, Glasgow S, Masui T, Henke R . A nonclassical bHLH Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling. Genes Dev. 2008; 22(2):166-78. PMC: 2192752. DOI: 10.1101/gad.1628008. View

2.
Brzezinski 4th J, Lamba D, Reh T . Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development. Development. 2010; 137(4):619-29. PMC: 2827615. DOI: 10.1242/dev.043968. View

3.
Glasgow S, Henke R, MacDonald R, Wright C, Johnson J . Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Development. 2005; 132(24):5461-9. DOI: 10.1242/dev.02167. View

4.
Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura Y . Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron. 2005; 47(2):201-13. DOI: 10.1016/j.neuron.2005.06.007. View

5.
Tavares I, Lima D . From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory system. J Anat. 2007; 211(2):261-8. PMC: 2375764. DOI: 10.1111/j.1469-7580.2007.00759.x. View