Gata3 controls the Development and Maintenance of Serotonergic Neuron Identity

FERNANDA DEFINO; BRUM, LUCIANO A.; NOELIA WEISSTAUB; SANTIAGO OLSZEVICKI; LANUZA GUILLERMO M

Congreso; Latin American Society for Developmental Biology Congress; 2019

The central serotonergic system modulates a wide range of brain functions, ranging from autonomic control and emotional responses to cognitive processes. During embryonic development, serotonergic neurons are produced from progenitors in the most ventral domain of hindbrain. During the last decade, genetic studies have identified that the transcription factors Pet1, Lmx1b and Gata3 are important for the proper assignment of serotonergic identity. By performing genetic tracings in young and adult mice in combination with expression analysis we found that Gata2 and Gata3 expression is retained in mature serotonergic neurons. To assess the role of Gata3 in adult Raphe neurons, we generated inducible Gata3 conditional knockouts and found reduced expression of Pet1, Tph2 and Sert in the dorsal raphe nucleus. Moreover, we found a decrease in serotonin synthesis, which is accompanied with a loss of habituation in open-field tests, showing behavioral consequences of 5HT neurons identity loss. Surprisingly, Gata3 deletion during serotoninergic neuron maturation showed no effects when analyzed in newborns but present similar effects in young/adult mice. These results indicate that Gata transcription factors not only are important for serotonergic neurons specification but are also involved in maintaining serotonergic identity throughout life.