{"id":1988,"date":"2009-07-17T00:00:00","date_gmt":"2009-07-17T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/timing-is-everything-growth-factor-keeps-brain-development-on-track\/"},"modified":"2023-12-10T00:15:16","modified_gmt":"2023-12-10T08:15:16","slug":"timing-is-everything-growth-factor-keeps-brain-development-on-track","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/timing-is-everything-growth-factor-keeps-brain-development-on-track\/","title":{"rendered":"Timing is everything: Growth factor keeps brain development on track"},"content":{"rendered":"<p>LA  JOLLA, CA\u2014Just like a conductor cueing musicians in an orchestra, Fgf10,  a member of the fibroblast growth factor (Ffg) family of morphogens, lets brain  stem cells know that the moment to get to work has arrived, ensuring that they  hit their first developmental milestone on time, report scientists at the Salk  Institute for Biological Studies in the July 16, 2009, edition of the journal <em>Neuron<\/em>.<\/p>\r\n<p>Their findings not only add new insights into  brain development and a novel function for Fgfs, but also reveal a possible  mechanism for the selective expansion of specific brain areas over the course  of evolution, such as the greatly increased size of the frontal lobe in humans.<\/p><div class=\"imageCaption\"><img decoding=\"async\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/03\/300_OlearySaharaJuly09_sci.jpg\" alt=\"Fgf10\" \/><p>Without Fgf10 (image on the right), neuronal stem cells fail to differentiate on time. As a consequence they keep multiplying generating a bigger pool of radial glia (shown in red), which in turn produce more neurons ultimately resulting in a larger cortex. Basal progenitors are shown in green.<\/p><p>\r\nImage: Courtesy of Dr. Setsuko Sahara, Salk Institute for Biological Studies.<\/p><\/div>\r\n<p>During  embryonic brain development, stem cells in charge of building the cortex\u2014the  largest brain structure and seat of most higher cognitive functions\u2014pass  through a series of tightly regulated stages: from omnipotent stem cell to  cortical progenitors cells capable of producing neurons.<\/p>\r\n<p>\"The timing of each of these transitions has  critical implications for brain development, since minor changes in the  proportion of progenitors exhibiting one or the other division mode at early  stages will result in substantial changes in the number of neurons and the size  of the cortex,\" says <a href=\"\/es\/faculty\/o'leary.html\/\">Dennis  O'Leary<\/a>, Ph.D., a professor in the Molecular Neurobiology Laboratory, who led  the study. <\/p>\r\n<p>Early in corticogenesis, stem cell-like  progenitor cells known as neuroepithelial cells under go symmetric cell  division, producing two identical progenitors to expand the pool of  neuroepithelial cells. Later on, they differentiate into more mature progenitor  cells referred to as radial glia, which then divide assymmetrically to produce  a pair of unlike daughter cells: one radial glia to maintain the pool of  progenitor cells and a cortical neuron or a basal progenitor. The latter will  migrate outward and then produce neurons to establish the superficial layers of  the cortex.<\/p>\r\n<p>But little is known about the mechanisms that  mediate the critical transition period that bridges the early expansion phase  of neuroepithelial cells and the later neurogenic phase, which produces all the  neurons that will eventually form the six layers of the cortex.<\/p><div class=\"imageCaption\"><img decoding=\"async\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/03\/300_OLEARYJune2009.jpg\" alt=\"Dennis  O'Leary and Setsuko Sahara\" \/><p>Dennis  O'Leary and Setsuko Sahara\r\n<\/p><\/div>\r\n<p>Initially, postdoctoral researcher and first  author Setsuko Sahara, Ph.D., was more interested in area patterning when she  started looking at the effects of deleting Fgf10 in mouse brain. But it quickly  became clear that the primary function of Fgf10 was to regulate the  differentiation of radial glia, a role that has significant implications for brain  size, including the size of specific cortical areas. \"These mice had  substantially enlarged brains,\" says Setsuko, \"but the structure was perfectly  fine.\" <\/p>\r\n<p>A closer look revealed that the transition from  the expansion stage to the neurogenic phase exhibited by cortical progenitors  was delayed by approximately two days. \"As  a consequence neuroepithelial cells keep multiplying generating a bigger pool  of radial glia, which in turn produce more neurons ultimately resulting in a  larger cortex,\" explains Sahara. Interestingly, the increase in size was limited  to the frontal cortex, demonstrating that at the time the population of early  progenitors was abnormally expanded in Fgf10 mutants, their area identity had  been fixed. <\/p>\r\n<p>\"These findings demonstrate a direct mechanism  employed during normal development to regulate brain size,\" says O'Leary.  \"These findings also have potential implications for how cortical areas have  evolved. Selectively expanding the progenitor pool by Fgf10 regulation of the  timing of radial glia differentiation could account for the selective expansion  of the frontal cortex, which has been greatly expanded in humans and is thought  to be important for evolving what are considered typically human traits.\" <\/p>\r\n<p>This work was supported by the National  Institutes of Health, the JSPS Fellowships for Research Abroad and the Uehara  Memorial Foundation.<\/p>\r\n\r\n<p><strong>About  the Salk Institute for Biological Studies<br \/>\r\n<\/strong>The Salk Institute for Biological Studies is one  of the world's preeminent basic research institutions, where internationally  renowned faculty probe fundamental life science questions in a unique, collaborative,  and creative environment. Focused both on discovery and on mentoring future  generations of researchers, Salk scientists make groundbreaking contributions  to our understanding of cancer, aging, Alzheimer's, diabetes, and  cardiovascular disorders by studying neuroscience, genetics, cell and plant  biology, and related disciplines.<\/p>\r\n<p>Faculty achievements have been recognized with  numerous honors, including Nobel Prizes and memberships in the National Academy  of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the  Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[103],"disease-research":[459],"class_list":["post-1988","disclosure","type-disclosure","status-publish","hentry","faculty-dennis-oleary","disease-research-glial-biology"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Timing is everything: Growth factor keeps brain development on track - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/timing-is-everything-growth-factor-keeps-brain-development-on-track\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Timing is everything: Growth factor keeps brain development on track - 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