title: Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development.
abstract: Trophoblast cells are the first lineage to form in the mammalian conceptus and mediate the process of implantation. We report the cloning of a basic helix-loop-helix (bHLH) transcription factor gene, Hxt, that is expressed in early trophoblast and in differentiated giant cells. A separate gene, Hed, encodes a related protein that is expressed in maternal deciduum surrounding the implantation site. Overexpression of Hxt in mouse blastomeres directed their development into trophoblast cells in blastocysts. In addition, overexpression of Hxt induced the differentiation of rat trophoblast (Rcho-1) stem cells as assayed by changes in cell adhesion and by activation of the placental lactogen-I gene promoter, a trophoblast giant cell-specific gene. In contrast, the negative HLH regulator, Id-1, inhibited Rcho-1 differentiation and placental lactogen-I transcription. These data demonstrate a role for HLH factors in regulating trophoblast development and indicate a positive role for Hxt in promoting the formation of trophoblast giant cells.
authors.affiliation: Department of Anatomy, University of California, San Francisco 94143, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Cross
authors.forename: M L
authors.initials: ML
authors.lastname: Flannery
authors.forename: M A
authors.initials: MA
authors.lastname: Blanar
authors.forename: E
authors.initials: E
authors.lastname: Steingrimsson
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: W J
authors.initials: WJ
authors.lastname: Rutter
authors.forename: Z
authors.initials: Z
authors.lastname: Werb
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D001755:Blastocyst / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D046508:Culture Techniques; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics; D004475:Ectoderm / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012097:Repressor Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors; C095572:Hand1 protein, mouse; C497455:Idb1 protein, mouse; C095575:transcription factor Hed