{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EMX2 is a homeobox transcription factor with diverse roles during development that span the central nervous system and beyond. In the developing brain, EMX2 is a key regulator of dorsal telencephalic patterning and neocortical arealization. Its activity is tightly controlled by upstream signals—in particular, direct regulation via WNT and BMP pathways through conserved enhancer elements (4) ensures appropriate graded expression in cortical progenitors. EMX2 contributes to the specification of cortical areas by repressing factors such as PAX6 in rostral regions (3,8), thereby modulating the balance of proliferative and neurogenic programs. In addition, EMX2 indirectly regulates FGF8 levels, which is critical for the proper positioning and size of primary sensory and motor areas as well as for hippocampal development (2,5). Cooperation with the related transcription factor EMX1 further underpins correct laminar organization, tangential migration, and axonal guidance in the developing neocortex, as revealed by the severe defects observed in Emx1/Emx2 double mutants (6,9)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its well‐established functions in cortical development, EMX2 is implicated in modulatory roles in other systems. For instance, it contributes to the formation and maintenance of the genital ridge during gonadal initiation (7). Moreover, in the adult olfactory system, although classically a nuclear transcription factor, EMX2 is also detected in axonal compartments where it interacts with translation regulators such as eIF4E—suggesting nonnuclear roles possibly related to localized control of protein synthesis (10). Finally, EMX2 may be involved in disease contexts; sequence‐dependent binding of EMX2 to regulatory elements is associated with altered transcription of key genes such as α‐synuclein, providing a potential link to Parkinson’s disease pathogenesis (1).\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, EMX2 functions as a pivotal transcriptional regulator integrating extracellular patterning signals with intrinsic genetic programs to control neurogenesis, cortical area specification, and non‐neuronal developmental processes, while its dosage and spatial expression are critical for establishing proper cell fate and regional identity."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Frank Soldner, Yonatan Stelzer, Chikdu S Shivalila, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature17939"}], "href": "https://doi.org/10.1038/nature17939"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27096366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27096366"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tomomi Shimogori, Victoria Banuchi, Hanyann Y Ng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.01428"}], "href": "https://doi.org/10.1242/dev.01428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15509764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15509764"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tadashi Hamasaki, Axel Leingärtner, Thomas Ringstedt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortex by direct specification of cortical progenitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2004.07.016"}], "href": "https://doi.org/10.1016/j.neuron.2004.07.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15294144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15294144"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Thomas Theil, Songül Aydin, Silke Koch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.129.13.3045"}], "href": "https://doi.org/10.1242/dev.129.13.3045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12070081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12070081"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tomomi Fukuchi-Shimogori, Elizabeth A Grove "}, {"type": "b", "children": [{"type": "t", "text": "Emx2 patterns the neocortex by regulating FGF positional signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn1093"}], "href": "https://doi.org/10.1038/nn1093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12872126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12872126"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kathie M Bishop, Sonia Garel, Yasushi Nakagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Neurol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cne.10549"}], "href": "https://doi.org/10.1002/cne.10549"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12561075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12561075"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yueh-Chiang Hu, Leah M Okumura, David C Page "}, {"type": "b", "children": [{"type": "t", "text": "Gata4 is required for formation of the genital ridge in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1003629"}], "href": "https://doi.org/10.1371/journal.pgen.1003629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23874227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23874227"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jian Sun, Shira Rockowitz, Qing Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory networks during forebrain and lens development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkv589"}], "href": "https://doi.org/10.1093/nar/gkv589"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26138486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26138486"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Koji Shinozaki, Toshihiko Miyagi, Michio Yoshida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of Cajal-Retzius cells and subplate neurons associated with defects of tangential cell migration from ganglionic eminence in Emx1/2 double mutant cerebral cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.129.14.3479"}], "href": "https://doi.org/10.1242/dev.129.14.3479"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12091317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12091317"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Stéphane Nédélec, Isabelle Foucher, Isabelle Brunet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0403824101"}], "href": "https://doi.org/10.1073/pnas.0403824101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15247416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15247416"}]}]}]}