{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:40:04Z","timestamp":1776274804454,"version":"3.50.1"},"reference-count":59,"publisher":"The Company of Biologists","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:p>Brain nuclei are spatially organized collections of neurons that share functional properties. Despite being central to vertebrate brain circuitry, little is known about how nuclei are generated during development. We have chosen the chick midbrain oculomotor complex (OMC) as a model with which to study the developmental mechanisms of nucleogenesis. The chick OMC comprises two distinct cell groups: a dorsal Edinger-Westphal nucleus of visceral oculomotor neurons and a ventral nucleus of somatic oculomotor neurons. Genetic studies in mice and humans have established that the homeobox transcription factor gene PHOX2A is required for midbrain motoneuron development. We probed, in forced expression experiments, the capacity of PHOX2A to generate a spatially organized midbrain OMC. We found that exogenous Phox2a delivery to embryonic chick midbrain can drive a complete OMC molecular program, including the production of visceral and somatic motoneurons. Phox2a overexpression was also able to generate ectopic motor nerves. The exit points of such auxiliary nerves were invested with ectopic boundary cap cells and, in four examples, the ectopic nerves were seen to innervate extraocular muscle directly. Finally, Phox2a delivery was able to direct ectopic visceral and somatic motoneurons to their correct native spatial positions, with visceral motoneurons settling close to the ventricular surface and somatic motoneurons migrating deeper into the midbrain. These findings establish that in midbrain, a single transcription factor can both specify motoneuron cell fates and orchestrate the construction of a spatially organized motoneuron nuclear complex.<\/jats:p>","DOI":"10.1242\/dev.041251","type":"journal-article","created":{"date-parts":[[2010,3,9]],"date-time":"2010-03-09T07:47:54Z","timestamp":1268120874000},"page":"1205-1213","source":"Crossref","is-referenced-by-count":34,"title":["PHOX2A regulation of oculomotor complex nucleogenesis"],"prefix":"10.1242","volume":"137","author":[{"given":"Khaleda B.","family":"Hasan","sequence":"first","affiliation":[{"name":"Department of Neurobiology, The University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seema","family":"Agarwala","sequence":"additional","affiliation":[{"name":"Section of Neurobiology, University of Texas at Austin, Austin TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifton W.","family":"Ragsdale","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, The University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042606514752600_R1","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1242\/dev.00179","article-title":"A role for midbrain arcs in nucleogenesis","volume":"129","author":"Agarwala","year":"2002","journal-title":"Development"},{"key":"2021042606514752600_R2","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/B978-008045046-9.01074-3","article-title":"Midbrain patterning","volume-title":"Encyclopedia of Neuroscience","author":"Agarwala","year":"2009"},{"key":"2021042606514752600_R3","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1126\/science.1058624","article-title":"Sonic Hedgehog control of size and shape in midbrain pattern formation","volume":"291","author":"Agarwala","year":"2001","journal-title":"Science"},{"key":"2021042606514752600_R4","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1242\/dev.02850","article-title":"Regulation of ventral midbrain patterning by Hedgehog signaling","volume":"134","author":"Bayly","year":"2007","journal-title":"Development"},{"key":"2021042606514752600_R5","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1093\/brain\/awl161","article-title":"Neurological features of congenital fibrosis of the extraocular muscles type 2 with mutations in PHOX2A","volume":"129","author":"Bosley","year":"2006","journal-title":"Brain"},{"key":"2021042606514752600_R6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1749-8104-2-21","article-title":"Boundary cap cells constrain spinal motor neuron somal migration at motor exit points by a semaphorin-plexin mechanism","volume":"2","author":"Bron","year":"2007","journal-title":"Neural Dev."},{"key":"2021042606514752600_R7","doi-asserted-by":"crossref","first-page":"9961","DOI":"10.1523\/JNEUROSCI.23-31-09961.2003","article-title":"Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype","volume":"23","author":"Cheng","year":"2003","journal-title":"J. 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