{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:25:46Z","timestamp":1791170746319,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T00:00:00Z","timestamp":1362528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The homeodomain transcription factor Pitx3 is critical for the survival of midbrain dopaminergic (<jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content>) neurons. Pitx3\u2010deficient mice exhibit severe but selective developmental loss of <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> neurons, with accompanying locomotor deficits resembling those seen in Parkinson's disease (PD) models. Here, we identify specific <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> cell subpopulations that are consistently spared in adult Pitx3\u2010hypomorphic (aphakia) mice, demonstrating that Pitx3 is not indiscriminately required by all <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> neurons for their survival. In aphakia mice, virtually all surviving <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> neurons in the substantia nigra (SN) and the majority of neurons in the adjacent ventral tegmental area (VTA) also express calbindin\u2010D28k, a calcium\u2010binding protein previously associated with resistance to injury in PD and in animal models. Cell\u2010mapping studies in wild\u2010type mice revealed that Pitx3 is primarily expressed in the ventral SN, a region particularly susceptible to MPTP and other dopaminergic neurotoxins. Furthermore, Pitx3\u2010expressing SN cells are preferentially lost following MPTP treatment. Finally, SN <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> neurons in Pitx3 hemizygous mice show increased sensitivity when exposed to MPTP. Thus, SN <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> neurons are represented by at least two distinct subpopulations including MPTP\u2010resistant Pitx3\u2010autonomous, calbindin\u2010positive neurons, and calbindin\u2010negative Pitx\u20103\u2010dependent cells that display elevated vulnerability to toxic injury, and probably correspond to the subpopulation that degenerates in PD. Impairment of Pitx3\u2010dependent pathways therefore increases vulnerability of <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> neurons to toxic injury. Together, these data suggest a novel link between Pitx3 function and the selective pattern of <jats:styled-content style=\"fixed-case\">mDA<\/jats:styled-content> cell loss observed in PD.<\/jats:p>","DOI":"10.1111\/jnc.12160","type":"journal-article","created":{"date-parts":[[2013,1,19]],"date-time":"2013-01-19T09:24:42Z","timestamp":1358587482000},"page":"932-943","source":"Crossref","is-referenced-by-count":55,"title":["The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress"],"prefix":"10.1111","volume":"125","author":[{"given":"Kelvin C.","family":"Luk","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir V.","family":"Rymar","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pepijn","family":"van den Munckhof","sequence":"additional","affiliation":[{"name":"Unit\u00e9 genetique moleculaire Institut de recherches cliniques de Montreal Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Steriade","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panojot","family":"Bifsha","sequence":"additional","affiliation":[{"name":"Unit\u00e9 genetique moleculaire Institut de recherches cliniques de Montreal Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Drouin","sequence":"additional","affiliation":[{"name":"Unit\u00e9 genetique moleculaire Institut de recherches cliniques de Montreal Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas F.","family":"Sadikot","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01360.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01128"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.037"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.12.033"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2002.1182"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21947"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.03.008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(75)90849-5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4423-08.2009"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.8.1437"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087753"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901800310"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902396106"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-011-0349-2"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90232-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-12-03935.1987"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1992.tb24523.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903620308"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05118.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.02.015"},{"key":"e_1_2_8_25_1","first-page":"925","article-title":"Dopamine (3\u2010hydroxytyramine) and brain function","volume":"18","author":"Hornykiewicz O.","year":"1966","journal-title":"Pharmacol. 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