title: Lhx9 gene expression during early limb development in mice requires the FGF signalling pathway.
abstract: Lhx9 is a member of the LIM-homeodomain gene family necessary for the correct development of many organs including gonads, limbs, heart and the nervous system. In the context of limb development, Lhx9 has been implicated as an integrator for Fibroblast growth factor (FGF) and Sonic hedgehog (Shh) signalling required for proximal-distal (PD) and anterior-posterior (AP) development of the limb. Three splice variants of the Lhx9 transcript are expressed during development, two of which are predicted to act in a dominant negative fashion, competing with the DNA binding version of Lhx9 for binding to cofactors via the LIM-domain. We examined the expression pattern for the three alternative splice forms of Lhx9; Lhx9α, Lhx9β and Lhx9c during early limb development. We have found that of the three Lhx9 isoforms, only Lhx9α and Lhx9c (intact homeodomain) are expressed during early limb development, each with their own distinct expression pattern. Additionally we determined that Lhx9 expression overlaps with FGF10 expression in the developing limb bud mesenchyme. Limb bud explant cultures, in the presence of signalling pathway inhibitors, also indicated that Lhx9 mRNA expression in the limb bud was dependent on FGF signalling.
authors.affiliation: Developmental Biology and Genomics Laboratory, Department of Anatomy, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Developmental Biology and Genomics Laboratory, Department of Anatomy, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand. Electronic address: meganj.wilson@otago.ac.nz.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Wilson
mesh_terms: D000818:Animals; D005121:Extremities / Q000196:embryology; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000235:genetics; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D060850:LIM-Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics*; D018878:Limb Buds / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D060850:LIM-Homeodomain Proteins; C117058:Lhx9 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D005346:Fibroblast Growth Factors
keywords: Isoforms; LIM-homeodomain; Lhx9; Limb development; Regulation