title: A BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing hindbrain.
abstract: The divergent homeobox-containing transcription factor, Tlx-3 (also known as Hox11L2/Rnx), is required for proper formation of first-order relay sensory neurons in the developing vertebrate brainstem. To date, however, the inductive signals and transcriptional regulatory cascade underlying their development are poorly understood. We previously isolated the chick Tlx-3 homologue and showed it is expressed early (i.e. beginning at HH15) in distinct subcomponents of both the trigeminal/solitary and vestibular nuclei. Here we show via in vivo rhombomere inversions that expression of Tlx-3 is under control of local environmental signals. Our RNA in situ analysis shows expression of the BMP-specific receptor, Bmpr-1b, correlates well with Tlx-3. Furthermore, manipulation of the BMP signaling pathway in vivo via electroporation of expression vectors encoding either BMP or NOGGIN coupled with MASH1 gain-of-function experiments demonstrate that a BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing brainstem. Notably, high-level Noggin misexpression results in an increase in newly differentiated Tlx-3+ neurons that correlates with a corresponding increase in the number of Calretinin+ neurons in vestibular nuclei at later developmental stages strongly suggesting that Tlx-3, in addition to being required for proper formation of somatic as well as visceral sensory neurons in the trigeminal and solitary nuclei, respectively, is sufficient for proper formation of special somatic sensory neurons in vestibular nuclei.
authors.affiliation: Genes and Development Research Group, Department of Cell Biology and Anatomy, Institute of Maternal and Child Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada.
authors.forename: Amata
authors.initials: A
authors.lastname: Hornbruch
authors.forename: Grace
authors.initials: G
authors.lastname: Ma
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ballermann
authors.forename: Katerina
authors.initials: K
authors.lastname: Tumova
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Cairine Logan
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; C065500:ASCL1 protein, human; C099107:CASH-1 protein, Gallus gallus