title: Prep1.1 has essential genetic functions in hindbrain development and cranial neural crest cell differentiation.
abstract: In this study we analysed the function of the Meinox gene prep1.1 during zebrafish development. Meinox proteins form heterotrimeric complexes with Hox and Pbx members, increasing the DNA binding specificity of Hox proteins in vitro and in vivo. However, a role for a specific Meinox protein in the regulation of Hox activity in vivo has not been demonstrated. In situ hybridization showed that prep1.1 is expressed maternally and ubiquitously up to 24 hours post-fertilization (hpf), and restricted to the head from 48 hpf onwards. Morpholino-induced prep1.1 loss-of-function caused significant apoptosis in the CNS. Hindbrain segmentation and patterning was affected severely, as revealed by either loss or defective expression of several hindbrain markers (foxb1.2/mariposa, krox20, pax2.1 and pax6.1), including anteriorly expressed Hox genes (hoxb1a, hoxa2 and hoxb2), the impaired migration of facial nerve motor neurons, and the lack of reticulospinal neurons (RSNs) except Mauthner cells. Furthermore, the heads of prep1.1 morphants lacked all pharyngeal cartilages. This was not caused by the absence of neural crest cells or their impaired migration into the pharyngeal arches, as shown by expression of dlx2 and snail1, but by the inability of these cells to differentiate into chondroblasts. Our results indicate that prep1.1 has a unique genetic function in craniofacial chondrogenesis and, acting as a member of Meinox-Pbc-Hox trimers, it plays an essential role in hindbrain development.
authors.affiliation: Dipartimento di Biologia, Universita' di Padova, Via U. Bassi 58/B, 35131 Padova, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Deflorian
authors.forename: Natascia
authors.initials: N
authors.lastname: Tiso
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: Marino
authors.initials: M
authors.lastname: Bortolussi
authors.forename: Francesco
authors.initials: F
authors.lastname: Argenton
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D002356:Cartilage / Q000002:abnormalities / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D005775:Gastrula / Q000378:metabolism; D006257:Head / Q000002:abnormalities / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486618:PBX4 protein, human; C469732:Pbx2 protein, zebrafish; C486619:Pbx4 protein, zebrafish; C491412:Pknox1 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins