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==Evolution== {{See also|Pallium (neuroanatomy)#Evolution}} Of all the different brain regions, the cerebral cortex shows the largest evolutionary variation and has evolved most recently.<ref name="ReferenceA"/> In contrast to the highly conserved circuitry of the [[medulla oblongata]], for example, which serves critical functions such as regulation of heart and respiration rates, many areas of the cerebral cortex are not strictly necessary for survival. Thus, the evolution of the cerebral cortex has seen the advent and modification of new functional areas—particularly association areas that do not directly receive input from outside the cortex.<ref name="ReferenceA"/> A key theory of cortical evolution is embodied in the [[radial unit hypothesis]] and related [[Protomap (neuroscience)|protomap]] hypothesis, first proposed by Rakic.<ref>{{cite journal | vauthors = Rakic P | title = Specification of cerebral cortical areas | journal = Science | volume = 241 | issue = 4862 | pages = 170–176 | date = July 1988 | pmid = 3291116 | doi = 10.1126/science.3291116 | bibcode = 1988Sci...241..170R }}</ref> This theory states that new cortical areas are formed by the addition of new radial units, which is accomplished at the [[stem cell]] level. The protomap hypothesis states that the cellular and molecular identity and characteristics of neurons in each cortical area are specified by cortical [[stem cell]]s, known as [[radial glial cell]]s, in a primordial map. This map is controlled by secreted signaling [[protein]]s and downstream [[transcription factor]]s.<ref>{{cite journal | vauthors = Fukuchi-Shimogori T, Grove EA | title = Neocortex patterning by the secreted signaling molecule FGF8 | journal = Science | volume = 294 | issue = 5544 | pages = 1071–1074 | date = November 2001 | pmid = 11567107 | doi = 10.1126/science.1064252 | bibcode = 2001Sci...294.1071F | s2cid = 14807054 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bishop KM, Goudreau G, O'Leary DD | title = Regulation of area identity in the mammalian neocortex by Emx2 and Pax6 | journal = Science | volume = 288 | issue = 5464 | pages = 344–349 | date = April 2000 | pmid = 10764649 | doi = 10.1126/science.288.5464.344 | bibcode = 2000Sci...288..344B }}</ref><ref>{{cite journal | vauthors = Grove EA, Fukuchi-Shimogori T | title = Generating the cerebral cortical area map | journal = Annual Review of Neuroscience | volume = 26 | pages = 355–380 | date = 2003 | pmid = 14527269 | doi = 10.1146/annurev.neuro.26.041002.131137 | s2cid = 12282525 }}</ref>
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