title: Hmga2 is required for neural crest cell specification in Xenopus laevis.
abstract: HMGA proteins are small nuclear proteins that bind DNA by conserved AT-hook motifs, modify chromatin architecture and assist in gene expression. Two HMGAs (HMGA1 and HMGA2), encoded by distinct genes, exist in mammals and are highly expressed during embryogenesis or reactivated in tumour progression. We here addressed the in vivo role of Xenopus hmga2 in the neural crest cells (NCCs). We show that hmga2 is required for normal NCC specification and development. hmga2 knockdown leads to severe disruption of major skeletal derivatives of anterior NCCs. We show that, within the NCC genetic network, hmga2 acts downstream of msx1, and is required for msx1, pax3 and snail2 activities, thus participating at different levels of the network. Because of hmga2 early effects in NCC specification, the subsequent epithelial-mesenchymal transition (EMT) and migration of NCCs towards the branchial pouches are also compromised. Strictly paralleling results on embryos, interfering with Hmga2 in a breast cancer cell model for EMT leads to molecular effects largely consistent with those observed on NCCs. These data indicate that Hmga2 is recruited in key molecular events that are shared by both NCCs and tumour cells.
authors.affiliation: Dipartimento di Biologia, Unità di Biologia Cellulare e dello Sviluppo, Università degli Studi di Pisa, SS12 Abetone e Brennero 4, 56127 Pisa, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Macrì
authors.affiliation: Dipartimento di Biologia, Unità di Biologia Cellulare e dello Sviluppo, Università degli Studi di Pisa, SS12 Abetone e Brennero 4, 56127 Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Simula
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Trieste, via Giorgieri 5, 34127 Trieste, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Pellarin
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Trieste, via Giorgieri 5, 34127 Trieste, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pegoraro
authors.affiliation: Dipartimento di Biologia, Unità di Biologia Cellulare e dello Sviluppo, Università degli Studi di Pisa, SS12 Abetone e Brennero 4, 56127 Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Onorati
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Trieste, via Giorgieri 5, 34127 Trieste, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sgarra
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Trieste, via Giorgieri 5, 34127 Trieste, Italy.
authors.forename: Guidalberto
authors.initials: G
authors.lastname: Manfioletti
authors.affiliation: Dipartimento di Biologia, Unità di Biologia Cellulare e dello Sviluppo, Università degli Studi di Pisa, SS12 Abetone e Brennero 4, 56127 Pisa, Italy. Electronic address: robert.vignali@unipi.it.
authors.forename: Robert
authors.initials: R
authors.lastname: Vignali
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D025743:HMGA2 Protein / Q000235:genetics / Q000502:physiology*; D051957:MSX1 Transcription Factor / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D060172:Morpholinos / Q000235:genetics; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D025743:HMGA2 Protein; C515772:HMGA2 protein, Xenopus; D051957:MSX1 Transcription Factor; D060172:Morpholinos; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C489411:Pax3 protein, Xenopus; D034741:RNA, Small Interfering; C561115:SNAI2 protein, Xenopus; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins
keywords: Breast cancer; Epithelial–mesenchymal transition; HMGA2; Neural crest; Xenopus