Role of the Islet-1 transcription factor in the development of forebrain dopaminergic neurons

ADRIANA CAMARANO; VIVIANA F. BUMASCHNY; MILAGROS TROTTA; FLÁVIO S. J. DE SOUZA; CHASELON DOMINIQUE; MARCELO RUBINSTEIN

Ciudad Autónoma de Buenos Aires

Congreso; LASDB Meeting 2019 (Xth Meeting of the Latin American Society for Developmental Biology); 2019

Latin American Society for Developmental Biology

The hypothalamus is a forebrain region that regulates several basic homeostatic processes including reproduction, metabolism, energy balance, circadian rhythms, the response to stress and several behaviors. Its high anatomical complexity and location in the ventral forebrain has made it a difficult region to study. One transcription factor expressed during hypothalamic development is Islet-1 (Isl1), a member of the LIM-homeodomain family that regulates cell fate Specification in some neuronal populations of the arcuate nucleus, but its role in other areas has not been described. We observed that Isl1 coexpresses with the limiting enzyme for the synthesis of dopamine, tyrosine hydroxylase (TH) early in the developing forebrain and this coexpression continues during adult life. To elucidate the function that Isl1 exerts in the generation of theseneurons, we are employing a conditional knockout model which allows for the inactivation of the Isl1 gene at specific timepoints during mouse development. We focus specifically in the A13 population of dopaminergic neurons in the incertothalamic area, between the hypothalamus and the prethalamus. We show that the early deletion of Isl1 expression leads to the lack of TH in this area in early embryos. In later embryos, Isl1 elimination leads to a reduction in the size of the A13 nucleus and in the number of TH+ neurons. We postulate Isl1 as an important regulator of the dopaminergic fate in the hypothalamus and prethalamus.