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Interacción entre Hedgehog-Wnt en la Morfogénesis de la Glándula Submandibular en Ratones
Yunhong Song1, Yamin Chen2, Qian Wang1
1School of Stomatology, Quanzhou Medical College, Quanzhou, Fujian, China.
Genesis (New York, N.Y. : 2000)
|January 20, 2026
Resumen
El desarrollo de la glándula salival del ratón depende de la señalización Hedgehog (Hh). Este estudio revela que Hh reprime normalmente la actividad de Wnt, y la inhibición de Wnt puede rescatar los defectos causados por la alteración de la vía Hh.
Área de la Ciencia:
- Biología del Desarrollo
- Biología Molecular
- Señalización Celular
Sus antecedentes:
- El desarrollo de la glándula submandibular (SGM) de ratón es un modelo de morfogénesis ramificada.
- Sonic Hedgehog (Shh) es crucial para el desarrollo temprano de la SGM, pero sus efectos posteriores y las interacciones de la vía no se comprenden completamente.
Objetivo del estudio:
- Investigar la interacción funcional entre las señales Hedgehog (Hh) y Wnt durante la morfogénesis de la SGM.
- Esclarecer el papel de la señalización Hh en la regulación de la actividad de Wnt en las glándulas salivales en desarrollo.
Principales métodos:
- Inhibición farmacológica in vivo de la señalización Hh utilizando vismodegib en ratones embarazadas.
- Cultivo de órganos ex vivo de SGM con inhibidores de Hh y/o Wnt (vismodegib, XAV939).
- Análisis de la expresión génica (Ptch1, Gli1, Axin2, Lef1) y la localización de proteínas (β-catenina).
Principales resultados:
- La inhibición de Hh causó graves defectos morfológicos en la SGM, reducción de la ramificación y desorganización de los conductos.
- La supresión de Hh condujo a la regulación descendente de los genes diana de Hh y a la regulación ascendente de la actividad de la vía Wnt (aumento de β-catenina nuclear, elevación de la expresión de Axin2 y Lef1).
- La co-inhibición de la señalización Wnt rescató parcialmente los defectos de ramificación en cultivos de SGM con inhibición de Hh.
Conclusiones:
- La señalización Hedgehog (Hh) promueve la morfogénesis de la SGM murina al inhibir tónicamente la vía Wnt.
- Una novedosa diafonía inhibitoria entre la señalización Hh y Wnt es esencial para el desarrollo normal de la glándula salival.
- La comprensión de esta diafonía proporciona información sobre la organogénesis de la glándula salival y posibles dianas terapéuticas.
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