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Una teoría unificadora de la morfogénesis ramificada

Edouard Hannezo¹, Colinda L G J Scheele², Mohammad Moad³

¹Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK; The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QN, UK.

|September 23, 2017

Resumen

La ramificación compleja de órganos, como en las glándulas mamarias y los riñones, puede explicarse por un proceso auto-organizado simple. Las puntas equipotentes exploran el espacio, se ramifican y dejan de crecer cerca de los vecinos, creando estructuras intrincadas sin una programación genética rígida.

Área de la Ciencia:

Biología del desarrollo
Biología de sistemas
Biología matemática

Sus antecedentes:

La organogénesis de las estructuras ramificadas es compleja.
Se conocen las vías de señalización, pero las características macroscópicas siguen sin explicarse.

Objetivo del estudio:

Explicar las características macroscópicas de los órganos ramificados (tamaño, topología, patrón) dentro de un marco unificador.
Proponer un modelo para la morfogénesis auto-organizada en las estructuras epiteliales.

Principales métodos:

Análisis cuantitativo de las reconstrucciones de órganos a gran escala (glándula mamaria del ratón, riñón, próstata humana).
Mediciones de la cinética de la proliferación.
Modelado utilizando la ramificación y la aniquilación de caminatas aleatorias.

Principales resultados:

Las características macroscópicas de los órganos ramificados pueden explicarse cuantitativamente por un solo marco.
La morfogénesis surge de las puntas equipotentes que se ramifican estocásticamente y exploran el espacio.
Las puntas se vuelven inactivas cuando están cerca de los vecinos, lo que demuestra una competencia neutral por el espacio.

Conclusiones:

Las estructuras epiteliales ramificadas complejas se desarrollan a través de la autoorganización.
Una regla simple y genérica rige la morfogénesis, no una secuencia genética rígida.
La ramificación y la aniquilación de caminatas aleatorias proporcionan un marco unificador para el desarrollo de órganos.

Palabras clave:

ramificación y aniquilación de caminatas aleatorias Morfogénesis ramificada el riñón Glándula mamaria Modelado matemático la próstata autoorganización

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