{"id":48404,"date":"2022-04-28T11:00:00","date_gmt":"2022-04-28T09:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=48404"},"modified":"2024-03-22T12:56:53","modified_gmt":"2024-03-22T11:56:53","slug":"unravelling-the-origins-of-the-human-spine","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/unravelling-the-origins-of-the-human-spine\/","title":{"rendered":"Unravelling the origins of the human spine"},"content":{"rendered":"\n

The spinal column is the central supporting structure of the skeleton in all vertebrates. Not only does it provide a place for muscles to attach, it also protects the spinal cord and nerve roots. Defects in its development are known to cause rare hereditary diseases. Researchers from the Ebisuya Group<\/a> at EMBL Barcelona have now created a 3D in vitro <\/em>model that mimics how the precursor structures that give rise to the spinal column form during human embryonic development.<\/p>\n\n\n\n

The spinal column consists of 33 vertebrae, which form pairs of precursor structures called somites. Somites give rise to not only our vertebrae, but also our ribs and skeletal muscles. To ensure that these structures are formed correctly, somite development is tightly regulated, and each pair of somites arises at a particular sequential time point in development. This process is controlled by the segmentation clock, which is a group of genes that creates oscillatory waves, every wave giving rise to a new pair of somites.<\/p>\n\n\n\n

\u201cFor the first time, we have been able to create periodic pairs of human mature somites linked to the segmentation clock in the lab,\u201d said Marina Sanaki-Matsumiya, first author of the study published in Nature Communications<\/em><\/a>.  Using this approach, the researchers developed a 3D in vitro <\/em>model of human somite formation, also known as \u2018somitogenesis\u2019.<\/p>\n\n\n\n

Caption: Time lapse of repetitive somite formation. Credit: Ebisuya Group\/EMBL<\/figcaption><\/figure>\n\n\n\n

Creating a robust somitogenesis process<\/strong><\/h2>\n\n\n\n

The team cultured human induced pluripotent stem cells (hiPSC) in the presence of a cocktail of signalling molecules that induce cell differentiation. Three days later, the cells started to elongate and create anterior (top) and posterior (bottom) axes. At that point, the scientists added Matrigel to the culture mix. Matrigel is what some scientists call the magic powder: a protein mixture that is critical to many developmental processes. This process eventually led to the formation of somitoids \u2013 in vitro <\/em>equivalents of human somite precursor structures.<\/p>\n\n\n\n

To test whether the segmentation clock regulates somitogenesis in these somitoids, the researchers monitored the expression patterns of HES7<\/em>, the core gene involved in the process. They found clear evidence of oscillations, especially when somitogenesis was about to start. The somites that formed also had clear markers of epithelization \u2013 an important step in their maturation.<\/p>\n\n\n\n

Somite size matters<\/strong><\/h2>\n\n\n\n

The Ebisuya group studies how and why we humans are different from other species when it comes to embryonic development. One of the model systems they use to understand interspecies differences is the segmentation clock. In 2020, the group uncovered that the oscillation period<\/a> of the human segmentation clock is longer than the mouse segmentation clock.<\/p>\n\n\n\n

The current study also shows a link between the size of somites and the segmentation clock. \u201cThe somites that were generated had a constant size, independently of the number of cells used for the initial somitoid. The somite size did not increase even if the initial cell number did.\u201d explained Sanaki-Matsumiya.  \u201cThis suggests that the somites have a preferred species-specific size, which might be determined by local cell-cell interactions, the segmentation clock, or other mechanisms.\u201d<\/p>\n\n\n\n

To study this further, Miki Ebisuya and her group are now planning to grow somitoids of different species and compare them. The researchers are already working on several mammalian species, including rabbits, cattle, and rhinoceroses, setting up a \u2018stem cell zoo\u2019 in the lab.<\/p>\n\n\n\n

\u201cOur next project will focus on creating somitoids from different species, measure their cell proliferation and cell migration speed to establish what and how somitogenesis is different among species,\u201d said Ebisuya.<\/p>\n\n\n

\n\n\n

Descifrando los or\u00edgenes de la columna vertebral<\/strong><\/h1>\n\n\n\n

Cient\u00edficos del EMBL Barcelona recapitulan por primera vez en el laboratorio c\u00f3mo se forman secuencialmente las estructuras celulares que dan lugar a nuestra columna vertebral<\/h2>\n\n\n\n

La columna vertebral es la estructura central de soporte del esqueleto. No s\u00f3lo proporciona fijaci\u00f3n para los m\u00fasculos, sino que tambi\u00e9n protege la m\u00e9dula espinal y las ra\u00edces nerviosas. Se sabe que los defectos en su desarrollo causan enfermedades hereditarias raras.<\/p>\n\n\n\n

Investigadores del grupo de la Dra. Miki Ebisuya<\/a> del EMBL Barcelona crean un modelo 3D in vitro<\/em> que imita c\u00f3mo se forman las estructuras precursoras que dan lugar a la columna vertebral durante el desarrollo embrionario humano.<\/p>\n\n\n\n

La columna vertebral consta de 33 v\u00e9rtebras, que se forman a partir pares de estructuras precursoras llamadas somitas. Los somitas no s\u00f3lo dan lugar a las v\u00e9rtebras, sino tambi\u00e9n a las costillas y a los m\u00fasculos del esqueleto. Para garantizar la correcta formaci\u00f3n de estas estructuras, el desarrollo de los somitas est\u00e1 estrechamente regulado y cada par de somitas surge en un momento determinado del desarrollo. Este proceso est\u00e1 controlado por el reloj de segmentaci\u00f3n, que es un grupo de genes que crea ondas oscilantes, cada una de las cuales da lugar a un nuevo par de somitas.<\/p>\n\n\n\n

“Por primera vez, hemos podido crear en el laboratorio pares peri\u00f3dicos de somitas maduros humanos vinculadas al reloj de segmentaci\u00f3n”, afirma Marina Sanaki-Matsumiya, primera autora del estudio publicado en Nature Communications<\/em><\/a>.  Con este m\u00e9todo, los investigadores desarrollaron un modelo 3D in vitro de formaci\u00f3n de somitas humanos, tambi\u00e9n conocido como “somitog\u00e9nesis”.<\/p>\n\n\n\n

Creaci\u00f3n de un proceso de somitog\u00e9nesis robusto<\/strong><\/h2>\n\n\n\n

El equipo cultiv\u00f3 c\u00e9lulas madre humanas pluripotentes inducidas (hiPSC por sus siglas en ingl\u00e9s) con un c\u00f3ctel de mol\u00e9culas de se\u00f1alizaci\u00f3n que inducen la diferenciaci\u00f3n celular.<\/p>\n\n\n\n

Tres d\u00edas despu\u00e9s, los grupos de c\u00e9lulas comenzaron a alargarse y a crear ejes anteriores (arriba) y posteriores (abajo). En ese momento, los cient\u00edficos a\u00f1adieron Matrigel a la mezcla de cultivo. Matrigel es lo que algunos cient\u00edficos llaman el polvo m\u00e1gico: una mezcla de prote\u00ednas que es crucial para varios procesos del desarrollo. Este proceso condujo finalmente a la formaci\u00f3n de somitoides, que ser\u00edan los equivalentes in vitro<\/em> de las estructuras precursoras de los somitas humanos.<\/p>\n\n\n\n

Para comprobar si el reloj de segmentaci\u00f3n regula la somitog\u00e9nesis en estos somitoides, los investigadores controlaron los patrones de expresi\u00f3n de HES7<\/em>, el gen central implicado en el proceso. Encontraron claras evidencias de oscilaciones, especialmente cuando la somitog\u00e9nesis estaba a punto de comenzar. Los somitas que se formaron tambi\u00e9n ten\u00edan claros marcadores de epitelizaci\u00f3n, un paso importante en su maduraci\u00f3n.<\/p>\n\n\n\n

El tama\u00f1o del somita importa<\/strong><\/h2>\n\n\n\n

El grupo de investigaci\u00f3n liderado por la Dra. Miki Ebisuya estudia c\u00f3mo y por qu\u00e9 los humanos somos diferentes de otras especies en lo que respecta al desarrollo embrionario. Uno de los sistemas modelo de diferencias entre especies que utilizan es el reloj de segmentaci\u00f3n. En 2020, el grupo descubri\u00f3 que el periodo de oscilaci\u00f3n del reloj de segmentaci\u00f3n<\/a> humano es m\u00e1s largo que el del rat\u00f3n.<\/p>\n\n\n\n

El estudio actual tambi\u00e9n muestra una relaci\u00f3n entre el tama\u00f1o de los somitas y el reloj de segmentaci\u00f3n. “Los somitoides que creamos, independientemente del n\u00famero de c\u00e9lulas iniciales, ten\u00edan un tama\u00f1o de somita que era constante. No aumentaba aunque lo hiciera el n\u00famero de c\u00e9lulas iniciales”, explica Sanaki-Matsumiya.  “Esto sugiere que los somitas tienen un tama\u00f1o preferido, que podr\u00eda estar determinado por las interacciones locales c\u00e9lula-c\u00e9lula, el reloj de segmentaci\u00f3n u otros mecanismos”.<\/p>\n\n\n\n

Para profundizar en el estudio, Ebisuya y su grupo planean ahora cultivar somitoides de diferentes especies y compararlos. Los investigadores ya est\u00e1n trabajando con varias especies de mam\u00edferos, como conejos, bovinos y rinocerontes, creando un “zoo de c\u00e9lulas madre” en el laboratorio.<\/p>\n\n\n\n

“Nuestro pr\u00f3ximo proyecto se centrar\u00e1 en crear somitoides de diferentes especies, medir su proliferaci\u00f3n celular y la velocidad de migraci\u00f3n de las c\u00e9lulas para establecer qu\u00e9 y c\u00f3mo la somitog\u00e9nesis es diferente entre las especies”, dice Ebisuya.<\/p>\n","protected":false},"excerpt":{"rendered":"

Scientists at EMBL Barcelona have created for the first time a 3D in vitro model that recapitulates the periodic formation of human somites \u2013 structures that give rise to the spinal column.<\/p>\n","protected":false},"author":94,"featured_media":48410,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[497,1321,563,1748,5686,4776,431],"embl_taxonomy":[9762],"class_list":["post-48404","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-barcelona","tag-ebisuya","tag-embryonic-development","tag-press-release","tag-rare-disease","tag-segmentation-clock","tag-tissue-biology","embl_taxonomy-embl-barcelona"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","article_intro":"

EMBL Barcelona scientists have recapitulated for the first time in the laboratory how the cellular structures that give rise to our spinal column form sequentially<\/p>\n","related_links":[{"link_description":"Ebisuya Group","link_url":"https:\/\/www.embl.org\/groups\/ebisuya\/"},{"link_description":"Human and mouse cells run at different speed","link_url":"https:\/\/www.embl.org\/news\/science\/segmentation-clock\/"},{"link_description":"Tissue dynamics provide clues to human disease","link_url":"https:\/\/www.embl.org\/news\/science\/tissue-dynamics-provide-clues-to-human-disease\/"}],"source_article":[{"publication_title":"Periodic formation of epithelial somites from human pluripotent stem cells.","publication_link":{"title":"","url":"https:\/\/www.nature.com\/articles\/s41467-022-29967-1","target":""},"publication_authors":"Sanaki-Matsumiya M., et al.","publication_source":"Nature communications","publication_date":"28th April 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