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El gen homeobox LIM Lhx9 es esencial para la formación de las gónadas del ratón
O S Birk1, D E Casiano, C A Wassif
1Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA.
Nature
|March 8, 2000
Resumen
El gen homeobox LIM Lhx9 es crucial para el desarrollo de las gónadas en ratones. Su ausencia impide la formación de las gónadas, lo que lleva a que los ratones machos se desarrollen como hembras y sugiere un papel en la génesis gonadal humana.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Genética La genética.
- Biología Reproductiva Biología Reproductiva.
Sus antecedentes:
- Las gónadas de los mamíferos (ovarios y testículos) se desarrollan a partir de las crestas urogenitales.
- La determinación del sexo implica hormonas como la testosterona y la hormona anti-Mulleriana, producidas por los testículos.
- El gen homeobox LIM Lhx9 juega un papel en el desarrollo embrionario.
Objetivo del estudio:
- Para investigar la función del gen Lhx9 en el desarrollo de las gónadas de mamíferos.
- Determinar el papel de Lhx9 en la formación y diferenciación de las gónadas.
- Para explorar el vínculo potencial entre las mutaciones Lhx9 y la agenesia gonadal humana.
Principales métodos:
- Estudió la expresión génica Lhx9 en las crestas urogenitales de ratones durante el desarrollo embrionario.
- Se generaron y analizaron ratones carentes de Lhx9.9. funcional.
- Se evaluó la migración de células germinales, la proliferación de células somáticas y la formación de gónadas en embriones con deficiencia de Lhx9.
- Examinó la expresión del factor esteroideogénico 1 (Sf1) en mutantes Lhx9.
Principales resultados:
- Las transcripciones de Lhx9 están presentes en las crestas urogenitales tempranas y más tarde en la región intersticial de las gónadas en desarrollo.
- Los ratones con deficiencia de Lhx9 exhiben una migración normal de células germinales, pero no logran formar gónadas discretas debido a la falta de proliferación de células somáticas.
- Los ratones genéticamente machos con deficiencia de Lhx9 son fenotípicamente hembras, ya que carecen de testosterona y de la hormona anti-Mulleriana.
- La expresión del gen clave de la gonadogénesis Sf1 se reduce significativamente en las crestas genitales con deficiencia de Lhx9.
- Los mutantes Lhx9 no muestran otras anormalidades de desarrollo importantes.
Conclusiones:
- Lhx9 es esencial para la proliferación de las células somáticas y la formación de las gónadas.
- Lhx9 actúa aguas arriba de Sf1 en una cascada de desarrollo que regula la gonadogénesis.
- Las mutaciones en Lhx9 pueden ser una causa de agenesia gonadal aislada en humanos.
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