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http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/1470| Título : | A Boolean network model of human gonadal sex determination |
| Creador: | Osiris Ríos |
| Nivel de acceso: | Open access |
| Palabras clave : | Trastornos del Desarrollo Sexual 46, XY - patología Diferenciación Celular Linaje de la Célula Femenino Factor de Transcripción GATA4 - metabolismo Gónadas Células de la Granulosa - citología Humanos Masculino Modelos Biológicos Células de Sertoli - citología Procesos de Determinación del Sexo 46, XY Disorders of Sex Development - pathology Cell Differentiation Cell Lineage Female GATA4 Transcription Factor - metabolism Gonads Granulosa Cells - cytology Humans Male Models, Biological Sertoli Cells - cytology Sex Determination Processes Determinación del sexo Determinación sexual gonadal Modelo booleano Gene Red reguladora Sex determination Gonadal sex determination Boolean model Gene regulatory networ |
| Descripción : | Gonadal sex determination (GSD) in humans is a complex biological process that takes place in early stages of embryonic development when the bipotential gonadal primordium (BGP) differentiates towards testes or ovaries. This decision is directed by one of two distinct pathways embedded in a GSD network activated in a population of coelomic epithelial cells, the Sertoli progenitor cells (SPC) and the granulosa progenitor cells (GPC). In males, the pathway is activated when the Sex-Determining Region Y (SRY) gene starts to be expressed, whereas in females the WNT4/ β-catenin pathway promotes the differentiation of the GPCs towards ovaries. The interactions and dynamics of the elements that constitute the GSD network are poorly understood, thus our group is interested in inferring the general architecture of this network as well as modeling the dynamic behavior of a set of genes associated to this process under wild-type and mutant conditions. METHODS: We reconstructed the regulatory network of GSD with a set of genes directly associated with the process of differentiation from SPC and GPC towards Sertoli and granulosa cells, respectively. These genes are experimentally well-characterized and the effects of their deficiency have been clinically reported. We modeled this GSD network as a synchronous Boolean network model (BNM) and characterized its attractors under wild-type and mutant conditions. RESULTS: Three attractors with a clear biological meaning were found; one of them corresponding to the currently known gene expression pattern of Sertoli cells, the second correlating to the granulosa cells and, the third resembling a disgenetic gonad. CONCLUSIONS: The BNM of GSD that we present summarizes the experimental data on the pathways for Sertoli and granulosa establishment and sheds light on the overall behavior of a population of cells that differentiate within the developing gonad. With this model we propose a set of regulatory interactions needed to activate either the SRY or the WNT4/ β-catenin pathway as well as their downstream targets, which are critical for further sex differentiation. In addition, we observed a pattern of altered regulatory interactions and their dynamics that lead to some disorders of sex development (DSD). |
| Colaborador(es) u otros Autores: | Frias-Vázquez Sara Rodríguez Gómez Alfredo Kofman Susana Merchant-Larios Horacio Torres-Maldonado Leda and Mendoza-Sierra Luis |
| Fecha de publicación : | 2015 |
| Tipo de publicación: | Artículo |
| Formato: | |
| Identificador del Recurso : | 10.1186/s12976-015-0023-0 |
| Fuente: | Theoretical Biology and Medical Modelling 12(1):1-18 |
| URI : | http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/1470 |
| Idioma: | eng |
| Aparece en las colecciones: | Artículos |
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