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OTX2 restringe la entrada en la línea germinal del ratón

Jingchao Zhang1, Man Zhang2, Dario Acampora3

  • 1MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, Scotland.

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|October 5, 2018
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Resumen

OTX2 es un factor de transcripción crucial que regula el desarrollo de las células germinales. Su regulación a la baja permite la segregación oportuna de las células germinales primordiales (PGC) de las células somáticas, asegurando una reproducción adecuada.

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Área de la Ciencia:

  • Biología del desarrollo
  • Biología celular
  • La genética

Sus antecedentes:

  • La segregación de las células germinales es esencial para la reproducción.
  • Las células germinales primordiales (PGC) se desarrollan a partir del epiblasto en ratones.
  • Se sabe que la señalización BMP4 y los factores de transcripción de PGC están involucrados en la inducción de PGC.

Objetivo del estudio:

  • Investigar los mecanismos moleculares que conectan la señalización BMP4 con la inducción del factor de transcripción PGC.
  • Identificar los reguladores clave involucrados en la segregación de las células germinales de los linajes somáticos.
  • Para aclarar el papel de OTX2 en el desarrollo de la célula germinal primordial.

Principales métodos:

  • Estudios in vitro e in vivo relacionados con la deleción de Otx2 en ratones.
  • Análisis de la diferenciación y la competencia de las células de tipo PGC.
  • Investigación de la entrada de la línea germinal independiente de las señales de citoquinas y BLIMP1.

Principales resultados:

  • La regulación a la baja de OTX2 precede al inicio del programa PGC.
  • La deleción de Otx2 in vitro mejora la diferenciación celular similar a la del PGC y prolonga la competencia.
  • La deleción de Otx2 in vivo aumenta el número de PGC.
  • La pérdida de OTX2 hace que la diferenciación de PGC sea independiente de las citoquinas y de BLIMP1.

Conclusiones:

  • OTX2 actúa como un regulador represivo aguas arriba de los factores de transcripción de PGC.
  • OTX2 funciona como un obstáculo, limitando la entrada de la línea germinal a una ventana temporal y espacial específica.
  • Esto asegura la correcta segregación numérica de las células germinales del soma.