{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Doublesex and mab‐3–related transcription factor 3 (DMRT3) is a highly conserved transcription factor with key roles in the development and function of neural circuits that control locomotion and other developmental processes. In mammals, DMRT3 is expressed in a specific subdivision of spinal interneurons (dI6) and is indispensable for the proper assembly of central pattern generators (CPGs) that govern left–right coordination of limb movements during locomotion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In horses, a premature stop codon in DMRT3—often termed the “gait keeper” mutation—disrupts normal DMRT3 function and has been strongly linked to the ability to perform alternate gaits, yielding enhanced harness racing performance. This mutation has been detected at appreciable frequencies in several breeds and is a clear example of how subtle changes in DMRT3 can be harnessed by selective breeding to influence locomotor traits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its well‐documented role in locomotor circuitry, DMRT3 has been implicated in aspects of brain development. Its graded expression in the developing cerebral cortex and its interplay with other DMRT family members—for example, DMRT5—suggest that it participates in the fine tuning of cortical patterning and neuronal migration, thereby contributing to the proper formation of neocortical architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, candidate gene studies in reproductive disorders and in non‐mammalian species have provided preliminary evidence that DMRT3 (and its orthologues) may play additional roles in gonadal differentiation and fertility. For instance, rare variants in DMRT3 have emerged as potential contributors to primary ovarian insufficiency and male reproductive traits, underscoring its multifunctional and evolutionarily conserved nature."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, DMRT3 functions as a pivotal transcriptional regulator: it configures spinal circuits that coordinate gait, contributes to cortical patterning during brain development, and may influence reproductive processes. Its diverse roles across species exemplify how genetic variation in a single regulatory gene can have profound and far‐reaching phenotypic effects.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "b", "children": [{"type": "t", "text": "Citations:"}]}]}, {"type": "t", "text": "\n <ul>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "</li>\n <li>"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "</li>\n </ul>"}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lisa S Andersson, Martin Larhammar, Fatima Memic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11399"}], "href": "https://doi.org/10.1038/nature11399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22932389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22932389"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sharn Perry, Martin Larhammar, Jennifer Vieillard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0326-18.2018"}], "href": "https://doi.org/10.1523/JNEUROSCI.0326-18.2018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30578339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30578339"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Miguel Angel Ayala-Valdovinos, Jorge Galindo-García, David Sánchez-Chiprés, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel simple genotyping assay for detection of the 'Gait keeper' mutation in DMRT3 and allele frequencies in Azteca and Costa Rican Saddle Horse breeds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Probes (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mcp.2019.101506"}], "href": "https://doi.org/10.1016/j.mcp.2019.101506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31917254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31917254"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Laura Kvist, Johanna Honka, Markku Niskanen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selection in the Finnhorse, a native all-around horse breed."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Anim Breed Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jbg.12524"}], "href": "https://doi.org/10.1111/jbg.12524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33226152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33226152"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anne Ricard, Arnaud Duluard "}, {"type": "b", "children": [{"type": "t", "text": "Genomic analysis of gaits and racing performance of the French trotter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Anim Breed Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jbg.12526"}], "href": "https://doi.org/10.1111/jbg.12526"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33249655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33249655"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sarah De Clercq, Marc Keruzore, Elodie Desmaris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DMRT5 Together with DMRT3 Directly Controls Hippocampus Development and Neocortical Area Map Formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cereb Cortex (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cercor/bhw384"}], "href": "https://doi.org/10.1093/cercor/bhw384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28031177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28031177"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Takako Kikkawa, Nobuyuki Sakayori, Hayato Yuuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dmrt genes participate in the development of Cajal-Retzius cells derived from the cortical hem in the telencephalon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.156"}], "href": "https://doi.org/10.1002/dvdy.156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32012381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32012381"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "I Bestetti, C Barbieri, A Sironi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/deab192"}], "href": "https://doi.org/10.1093/humrep/deab192"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34480478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34480478"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Michela Ablondi, Susanne Eriksson, Sasha Tetu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic Divergence in Swedish Warmblood Horses Selected for Equestrian Disciplines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes10120976"}], "href": "https://doi.org/10.3390/genes10120976"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31783652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31783652"}]}]}]}