Transcriptional control of sexual differentiation of the nervous system
Identifying and understanding the genetic factors linked to neuropsychiatric disorders is a fundamental goal in neuroscience. The nervous system of male and females is sexually dimorphic at the molecular and structural levels and these differences lead to sex biases in the age of onset, prevalence, symptomatology and treatment for nearly every neuropsychiatric disorder. The general aim of our laboratory is to decipher the genetic and molecular mechanisms that control sex dimorphic configurations of the nervous system. Most sex differences are caused by sex hormones, however there is robust evidence that points to genetic factors also contributing to sexual dimorphisms.
The family of Dmrt transcription factors (TFs) has been identified as a common theme in the specification of sex-specific traits across distant animal species, including nematodes, flies and vertebrates. Our previous work and others in C. elegans and Drosophila, have established that Dmrt genes control the sexual differentiation of the nervous system. However, the role of Dmrts in the vertebrate nervous system has not been profusely investigated. We are approaching this question by characterizing the expression of the Dmrt genes in the mouse brain in a sex specific manner, to discover novel sexual-dimorphisms -linked to the Dmrt expression- and to understand the function of these TFs in the establishment and maintenance of mouse nervous system dimorphic configurations.
In summary, we will follow a multidisciplinary approach that will have important implications in the field: 1) it will reveal the high level of conservation of Dmrts as “master regulators of sexual dimorphisms” from nematodes to mouse; 2) it will identify novel mechanisms in the generation of sexually dimorphic configurations of the mouse brain that may be independent of sex hormones; 3) it will define novel brain dimorphic regions that could only be revealed by the analysis of molecular profiles in restricted cell types and 4) it could have clinical implications by uncovering novel genetic components linked to mental disorders.
Figure 1. DMRT5 expression in the mouse olfactory epithelium.
|Last name||Name||Laboratory||Ext.*||Professional category|
|Bermejo Santos||Ana||420||4693||abermejo(at)cbm.csic.es||Titulado Sup. Actividades Tecn. y Prof.GP1|
|Casado Navarro||Rafael||420||4693||rcasado(at)cbm.csic.es||Titulado Sup. Actividades Tecn. y Prof.GP1|
|Torrillas de la Cal||Rodrigo||420||4693||rtorrillas(at)cbm.csic.es||GJ-AI y TL_Titulado Sup. Actividades Técn. y Prof.GP1|
- Leyva-Diaz E, Masoudi N, Serrano-Saiz E, Glenwinkel L and Hobert O. Brn3/POU-IV-type POU homeobox genes – paradigmatic regulators of neuronal identity across phylogeny. WIREs Developmental Biology. 2020 Feb 3:e374
- Pereira L, Aeschimann F, Wang C, Lawson H, Serrano-Saiz E, Portman D, Grosshans H, Hobert O. Timing mechanism of sexually dimorphic nervous system differentiation. eLife, 2019 Jan 1;8.
- Serrano-Saiz E*, Leyva-Diaz E, De la Cruz E, Hobert O*. BRN3A-type POU homeobox genes maintain the identity of mature postmitotic neurons in nematodes and mice. Current Biology, 2018 Sep 10;28(17):2813-2823
- Serrano-Saiz E*, Oren-Suissa M and Hobert O*. Sexually dimorphic differentiation of a C. elegans hub neuron is cell-autonomously controlled by a conserved transcription factor. Current Biology, 2017 Jan 23;27(2):199-209. (F1000 recommended)
- Serrano-Saiz E*, Poole R, Felton T, Feifan Zhang, De la Cruz E, Hobert O*. Modular control of glutamatergic neuronal identity in C. elegans by distinct homeodomain proteins. Cell, 2013 Oct 24;155(3):659-73
* co-corresponding author
- Spanish Ministry of Economy and Business (MINECO) – (Programa Generación de conocimiento, 2018-2021)
- Comunidad de Madrid, Programa de Garantía Juvenil 2019 – Ayudante de Investigación
- Comunidad de Madrid, Programa de Garantía Juvenil 2019 – Investigador predoctoral