Scientists from the RIKEN Center for Biosystems Dynamics Research, EMBL Barcelona, Universitat Pompeu Fabra, and Kyoto University have found that the rhythmic signal of the segmentation clock \u2013 a genetic network that governs the sequential formation of the body pattern in embryos \u2013 beats more slowly in humans than in mice. The difference is due to certain biochemical reactions progressing in human cells at a lower rate.<\/p>\n\n\n\n
In the early phase of vertebrate development, the embryo develops into a series of segments that eventually differentiate into various types of tissues, such as muscles or bones. This process is governed by an oscillating biochemical process, known as the segmentation clock, which varies in speed between species. In mice, each oscillation of the segmentation clock takes about two hours, while in human cells it takes five hours. However, why the length of this cycle varies between species has remained a mystery.<\/p>\n\n\n\n
To solve this enigma, the researchers used mouse embryonic stem cells and human induced pluripotent stem (iPS) cells \u2013 both of which have the ability to specialise to form other cell types in the body. The researchers transformed them into a cell type known as presomitic mesoderm (PSM), whose development is governed by the segmentation clock.<\/p>\n\n\n\n
The scientists first examined whether the difference in oscillation frequency between the two cell types was due to the ways that multiple cells communicate with each other, or instead could be found in the biochemical processes within each individual cell. Using experiments that either isolated cells or blocked important signals, they found out that it was the biochemical processes within individual cells that were responsible.<\/p>\n\n\n\n
Once it was clear that the key processes governing segmentation clock oscillations occurred inside the cells, the researchers suspected that the difference might be due to a master gene called HES7<\/em>. They performed a number of experiments in which they swapped the HES7<\/em> genes between human cells and mouse cells, but to their surprise this did not affect the cycle.<\/p>\n\n\n\n \u201cFailing to show a difference in the gene expression left us with the possibility that the difference in oscillation frequency was driven by different biochemical reactions within the cells,\u201d says corresponding author Miki Ebisuya, Group Leader at EMBL Barcelona, who performed the work at RIKEN BDR and at EMBL.<\/p>\n\n\n\n But what exactly were these differences? To find out, the team looked at the degradation rate of the HES7 protein, which plays a key role in the oscillation cycle in both mice and humans. They observed that both the human and the mouse version of the HES7 protein were degraded more slowly in human cells than in mouse cells. They also discovered that the time it took cells to transcribe the HES7<\/em> gene into messenger RNA (mRNA), to process the mRNA molecule, and to translate it into proteins was significantly different. \u201cWe could thus show that it was indeed the cellular environment in human and mouse cells that made the difference in the biochemical reaction speeds, and thus in the time scales involved,\u201d says Ebisuya.<\/p>\n\n\n\n As Ebisuya explains, their observations led the scientists to develop the concept of \u2018developmental allochrony\u2019, a term that means something develops over different times. \u201cOur study will help us to understand the complicated process through which vertebrates develop,\u201d says Ebisuya. \u201cOne of the key remaining questions we\u2019d like to answer is what exactly drives the differences in reaction rates in mouse and human cells. We plan to shed light on this mystery in the near future.\u201d <\/p>\n\n\n Cient\u00edficos del Centro de Investigaci\u00f3n de Din\u00e1mica de Biosistemas RIKEN, del EMBL Barcelona, \u200b\u200bde la Universitat Pompeu Fabra y de la Universidad de Kyoto han descubierto que la se\u00f1al r\u00edtmica del \u201creloj de segmentaci\u00f3n\u201d, una red de genes que gobierna la formaci\u00f3n secuencial del patr\u00f3n corporal en embriones, late m\u00e1s lento en humanos que en ratones. La diferencia se debe a que algunas reacciones bioqu\u00edmicas en las c\u00e9lulas humanas progresan a un ritmo menor.<\/p>\n\n\n\n En la fase inicial del desarrollo de los vertebrados, el embri\u00f3n se desarrolla en una serie de segmentos que finalmente se diferencian en varios tipos de tejidos, como m\u00fasculos o huesos. Este proceso se rige por un proceso bioqu\u00edmico oscilante, conocido como \u201creloj de segmentaci\u00f3n\u201d, que var\u00eda en velocidad seg\u00fan la especie. En ratones, cada oscilaci\u00f3n del reloj de segmentaci\u00f3n tarda unas dos horas, mientras que en las c\u00e9lulas humanas tarda cinco horas. Sin embargo, sigue siendo un misterio el motivo por el cual la duraci\u00f3n de este ciclo es diferente entre las distintas especies.<\/p>\n\n\n\n Para resolver este enigma, los investigadores han utilizado c\u00e9lulas madre embrionarias de rat\u00f3n y c\u00e9lulas madre pluripotentes inducidas humanas (iPS). Ambas tienen la capacidad de especializarse para formar otros tipos de c\u00e9lulas en el cuerpo. Los cient\u00edficos las han transformado en un tipo celular conocido como mesodermo presom\u00edtico (PSM), cuyo desarrollo est\u00e1 regido por el \u00a8reloj de segmentaci\u00f3n\u00a8.<\/p>\n\n\n\n Primero, los cient\u00edficos han estudiado si la diferencia en la frecuencia de oscilaci\u00f3n entre los dos tipos de c\u00e9lulas se debe a la forma en la que las c\u00e9lulas se comunican entre s\u00ed, o si el origen de la discrepancia se encuentra en los procesos bioqu\u00edmicos dentro de cada c\u00e9lula. Mediante experimentos de aislamiento de c\u00e9lulas o de bloqueo de se\u00f1ales importantes, se han dado cuenta de que son los procesos bioqu\u00edmicos dentro de las c\u00e9lulas los que causan las diferentes frecuencias.<\/p>\n\n\n\n Una vez confirmado que los procesos clave que gobiernan las oscilaciones del reloj de segmentaci\u00f3n ocurren dentro de las c\u00e9lulas, los investigadores comenzaron a sospechar que la diferencia en los ritmos de desarrollo podr\u00eda deberse a un gen llamado HES7. Sin embargo, para su sorpresa, una serie de experimentos en los que intercambiaron los genes HES7 entre c\u00e9lulas humanas y c\u00e9lulas de rat\u00f3n no afect\u00f3 la duraci\u00f3n del ciclo.<\/p>\n\n\n\n \u201cNo haber sido capaces de mostrar una diferencia en la expresi\u00f3n g\u00e9nica nos dej\u00f3 con la \u00fanica posibilidad de que la diferencia en la frecuencia de oscilaci\u00f3n se debiera a las diferentes reacciones bioqu\u00edmicas dentro de las c\u00e9lulas\u201d, comenta Miki Ebisuya, quien actualmente se desempe\u00f1a como l\u00edder de grupo en EMBL Barcelona , \u200b\u200by que ha realizado el trabajo en el RIKEN BDR y en el EMBL.<\/p>\n\n\n\n Pero, \u00bfen qu\u00e9 consisten exactamente estas diferencias? Para averiguarlo, el equipo ha examinado la tasa de degradaci\u00f3n de la prote\u00edna HES7, que desempe\u00f1a un papel clave en el ciclo de oscilaci\u00f3n, tanto en ratones como en humanos. Y han observado que la prote\u00edna HES7 se degrada m\u00e1s lentamente en c\u00e9lulas humanas que en c\u00e9lulas de rat\u00f3n. Tambi\u00e9n han descubierto que el tiempo que tardan las c\u00e9lulas en transcribir el gen HES7 en ARN mensajero (ARNm), procesar la mol\u00e9cula de ARNm y traducirlo en prote\u00ednas es significativamente diferente. \u201cDe este modo, hemos podido demostrar que es el entorno celular de las c\u00e9lulas humanas y de rat\u00f3n el que marca la diferencia en las velocidades de reacci\u00f3n bioqu\u00edmica y, por tanto, en las escalas de tiempo implicadas\u201d, asevera Ebisuya.<\/p>\n\n\n\n Como explica Ebisuya, sus observaciones han llevado a los cient\u00edficos a desarrollar el concepto de \u201calocron\u00eda del desarrollo\u201d, un t\u00e9rmino que significa que algo se desarrolla en escalas de tiempos diferentes. \u201cNuestro estudio nos ayudar\u00e1 a comprender el complicado proceso a trav\u00e9s del cual se desarrollan los vertebrados\u201d, a\u00f1ade Ebisuya. \u201cUna de las preguntas clave que queda pendiente y que nos gustar\u00eda responder es a qu\u00e9 se deben exactamente las diferencias en las tasas de reacci\u00f3n en las c\u00e9lulas humanas y en las de rat\u00f3n. Queremos arrojar luz sobre este misterio en un futuro pr\u00f3ximo\u201d.<\/p>\n","protected":false},"excerpt":{"rendered":" The internal clock that governs the development of embryos ticks slower for humans than for mice. Differences in the speed of biochemical reactions underlie the differences between species in the tempo of development.<\/p>\n","protected":false},"author":105,"featured_media":32278,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[497,50,64,1321,563,4776],"embl_taxonomy":[19237],"class_list":["post-32244","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-barcelona","tag-biochemistry","tag-cell-biology","tag-ebisuya","tag-embryonic-development","tag-segmentation-clock","embl_taxonomy-ebisuya-group-visiting"],"acf":{"featured":true,"show_featured_image":false,"color":"#563d82","link_color":"#fff","article_intro":" EMBL scientists uncover the biochemical mechanisms that govern the tempo of embryo development<\/p>\n","related_links":[{"link_description":"Research in the Ebisuya Group","link_url":"https:\/\/www.embl.es\/research\/unit\/ebisuya\/index.html"}],"article_sources":[{"source_description":" Matsuda, M et al. Science<\/em>, published online 18 September 2020. DOI: 10.1126\/science.aba7668<\/p>\n","source_link_url":"https:\/\/science.sciencemag.org\/cgi\/doi\/10.1126\/science.aba7668"}],"in_this_article":false,"youtube_url":"https:\/\/www.youtube.com\/embed\/zf4zhI-RwV0","mp4_url":"","video_caption":"Cells in a developing organism have an inbuilt clock called the segmentation clock. EMBL Barcelona researchers now uncovered the biochemical mechanisms that govern the tempo of this clock. VIDEO: Miki Ebisuya\/EMBL","press_contact":"EMBL Generic","translations":[{"translation_language":"Spanish","translation_anchor":"#spanish"}],"vf_locked":false,"embl_taxonomy_term_who":false,"embl_taxonomy_term_what":false,"embl_taxonomy_term_where":2882},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"18a7a17b-e276-4afd-b0ca-8ddac1883d45\";i:2;s:36:\"8e848d63-b947-49ca-a00b-53af531ad40b\";}","parents":[],"name":["Ebisuya Group (Visiting)"],"slug":"ebisuya-group-visiting","description":"What > Tissue biology and disease modelling > Ebisuya Group (Visiting)"}],"yoast_head":"\nTowards a better understanding of vertebrate development<\/h3>\n\n\n\n
\n\n\n\n\n\n\nEl reloj del desarrollo de las c\u00e9lulas humanas y de los ratones funciona a velocidades diferentes<\/strong><\/h1>\n\n\n\n
El reloj interno que gobierna el desarrollo de los embriones es m\u00e1s lento en los humanos que en los ratones. Las diferencias entre las especies en cuanto al ritmo de desarrollo se basan en la velocidad de sus reacciones bioqu\u00edmicas.<\/h2>\n\n\n\n
Cada especie a su ritmo<\/h3>\n\n\n\n
Velocidades de reacci\u00f3n bioqu\u00edmica diferentes explican por qu\u00e9 los ratones se desarrollan m\u00e1s r\u00e1pido que los humanos<\/h3>\n\n\n\n
Hacia una mejor comprensi\u00f3n del desarrollo de los vertebrados<\/h3>\n\n\n\n