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Regulación genética y mecánica del desarrollo de los músculos lisos intestinales
Tyler R Huycke1, Bess M Miller2, Hasreet K Gill1
1Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell
|September 21, 2019
Resumen
Las capas de músculo liso intestinal embrionario se forman a través de una combinación de vías de señalización y fuerzas mecánicas. La señalización de Hedgehog y Bone Morphogenetic Protein (BMP) guía el patrón inicial, mientras que los estímulos mecánicos del crecimiento diferencial y las contracciones musculares dirigen la alineación celular.
Área de la Ciencia:
- Biología del desarrollo
- Fisiología gastrointestinal
- Ingeniería de tejidos
Sus antecedentes:
- El tracto gastrointestinal posee estructuras musculares lisas complejas y estratificadas que son cruciales para su funcionamiento.
- Los mecanismos subyacentes al patrón y alineación precisos de estas capas de músculo liso embrionario siguen siendo poco conocidos.
Objetivo del estudio:
- Elucidar los mecanismos moleculares y mecánicos que rigen la formación y alineación de las capas de músculo liso en el tracto gastrointestinal en desarrollo.
- Para vincular las vías de señalización del morfógeno con las señales mecánicas en la dirección de la organización de las células musculares lisas.
Principales métodos:
- Investigó las funciones de las vías de señalización de Hedgehog y Bone Morphogenetic Protein (BMP) en el desarrollo de la capa muscular lisa.
- Analizó el impacto del crecimiento diferencial y las contracciones musculares espontáneas en la alineación de las células musculares lisas.
- Se utilizaron modelos embrionarios para observar y cuantificar la formación y orientación de la capa muscular.
Principales resultados:
- La señalización de erizo, mediada por BMP, define la posición de la capa muscular lisa circumferencial interna.
- La inhibición localizada de la BMP es esencial para la formación de la capa externa del músculo liso longitudinal.
- Las cepas residuales del crecimiento diferencial del tubo intestinal orientan la capa interna, mientras que sus contracciones alinean la capa externa.
Conclusiones:
- La organización de la capa de músculo liso en el intestino es el resultado de un patrón integrado impulsado por morfógenos y una alineación celular controlada mecánicamente.
- Este estudio proporciona un marco mecanicista para comprender la organización del músculo liso en varios órganos tubulares.
- Los hallazgos ofrecen información sobre posibles defectos de desarrollo y estrategias terapéuticas para trastornos de la motilidad gastrointestinal.
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