Inactivation of the GATA Cofactor ZFPM1 Results in Abnormal Development of Dorsal Raphe Serotonergic Neuron Subtypes and Increased Anxiety-Like Behavior

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Tikker , L , Casarotto , P , Singh , P , Biojone , C , Piepponen , T P , Estartus , N , Seelbach , A , Sridharan , R , Laukkanen , L , Castren , E & Partanen , J 2020 , ' Inactivation of the GATA Cofactor ZFPM1 Results in Abnormal Development of Dorsal Raphe Serotonergic Neuron Subtypes and Increased Anxiety-Like Behavior ' , Journal of Neuroscience , vol. 40 , no. 45 , pp. 8669-8682 . https://doi.org/10.1523/JNEUROSCI.2252-19.2020

Title: Inactivation of the GATA Cofactor ZFPM1 Results in Abnormal Development of Dorsal Raphe Serotonergic Neuron Subtypes and Increased Anxiety-Like Behavior
Author: Tikker, Laura; Casarotto, Plinio; Singh, Parul; Biojone, Caroline; Piepponen, T. Petteri; Estartus, Nuri; Seelbach, Anna; Sridharan, Ravindran; Laukkanen, Liina; Castren, Eero; Partanen, Juha
Other contributor: University of Helsinki, Developmental neurogenetics
University of Helsinki, Neuroscience Center
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Neuroscience Center
University of Helsinki, Regenerative pharmacology group
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Molecular and Integrative Biosciences Research Programme








Date: 2020-11-04
Language: eng
Number of pages: 14
Belongs to series: Journal of Neuroscience
ISSN: 0270-6474
DOI: https://doi.org/10.1523/JNEUROSCI.2252-19.2020
URI: http://hdl.handle.net/10138/336539
Abstract: Serotonergic neurons in the dorsal raphe (DR) nucleus are associated with several psychiatric disorders including depression and anxiety disorders, which often have a neurodevelopmental component. During embryonic development, GATA transcription factors GATA2 and GATA3 operate as serotonergic neuron fate selectors and regulate the differentiation of serotonergic neuron subtypes of DR. Here, we analyzed the requirement of GATA cofactor ZFPM1 in the development of serotonergic neurons using Zfpm1 conditional mouse mutants. Our results demonstrated that, unlike the GATA factors, ZFPM1 is not essential for the early differentiation of serotonergic precursors in the embryonic rhombomere 1. In contrast, in perinatal and adult male and female Zfpm1 mutants, a lateral subpopulation of DR neurons (ventrolateral part of the DR) was lost, whereas the number of serotonergic neurons in a medial subpopulation (dorsal region of the medial DR) had increased. Additionally, adult male and female Zfpm1 mutants had reduced serotonin concentration in rostral brain areas and displayed increased anxiety-like behavior. Interestingly, female Zfpm1 mutant mice showed elevated contextual fear memory that was abolished with chronic fluoxetine treatment. Altogether, these results demonstrate the importance of ZFPM1 for the development of DR serotonergic neuron subtypes involved in mood regulation. It also suggests that the neuronal fate selector function of GATAs is modulated by their cofactors to refine the differentiation of neuronal subtypes.
Subject: anxiety
differentiation
dorsal raphe
embryo
serotonergic neuron
transcription factor
ELEVATED PLUS-MAZE
CHROMATIN OCCUPANCY
VENTRAL HIPPOCAMPUS
MICE LACKING
FEAR
AMYGDALA
SYSTEM
MEMORY
FRIEND
FOG-2
3112 Neurosciences
3124 Neurology and psychiatry
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