The winged-helix transcription factor HNF-3β is required for notochord development in the mouse embryo

HNF-3 beta, a transcription factor of the winged-helix family, is expressed in embryonic and adult endoderm and also in midline cells of the node, notochord, and floor plate in mouse embryos. To define the function of HNF-3 beta, a targeted mutation in the HNF-3 beta locus was generated by homologous recombination in embryonic stem cells. Mice lacking HNF-3 beta die by embryonic day (E) 10-11. Mutant embryos examined from E6.5 to E9.5 do not form a distinct node and lack a notochord. In addition, mutant embryos show marked defects in the organization of somites and neural tube that may result from the absence of the notochord. The neural tube of mutant embryos exhibits overt anteroposterior polarity but lacks a floor plate and motor neurons. Endodermal cells are present but fail to form a gut tube in mutant embryos. These studies indicate that HNF-3 beta has an essential role in the development of axial mesoderm in mouse embryos.

[1]  P. Ingham,et al.  Axial, a zebrafish gene expressed along the developing body axis, shows altered expression in cyclops mutant embryos. , 1993, Genes & development.

[2]  C. Niehrs,et al.  Mesodermal patterning by a gradient of the vertebrate homeobox gene goosecoid. , 1994, Science.

[3]  A. Bradley.  Production and analysis of chimeric mice , 1987 .

[4]  S. Burley,et al.  Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5 , 1993, Nature.

[5]  K. G. Coleman,et al.  Expression of engrailed proteins in arthropods, annelids, and chordates , 1989, Cell.

[6]  H. Spemann.  Embryonic development and induction , 1938 .

[7]  Ken W. Y. Cho,et al.  Gastrulation in the mouse: The role of the homeobox gene goosecoid , 1992, Cell.

[8]  J. Darnell,et al.  Transcriptional control of the mouse prealbumin (transthyretin) gene: both promoter sequences and a distinct enhancer are cell specific , 1986, Molecular and cellular biology.

[9]  K. Theiler.  Anatomy and development of the "truncate" (boneless) mutation in the mouse. , 1959, The American journal of anatomy.

[10]  P. Gruss,et al.  Altered Pax gene expression in murine notochord mutants: the notochord is required to initiate and maintain ventral identity in the somite , 1993, Mechanisms of Development.

[11]  D Weigel,et al.  The fork head domain: A novel DNA binding motif of eukaryotic transcription factors? , 1990, Cell.

[12]  T. Jessell,et al.  Mesodermal control of neural cell identity: floor plate induction by the notochord. , 1990, Science.

[13]  B. Hogan,et al.  Embryonic expression of Lim-1, the mouse homolog of Xenopus Xlim-1, suggests a role in lateral mesoderm differentiation and neurogenesis. , 1994, Developmental biology.

[14]  J. Gerhart,et al.  Planar induction of anteroposterior pattern in the developing central nervous system of Xenopus laevis. , 1992, Science.

[15]  M. Jamrich,et al.  A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain. , 1992, Genes & development.

[16]  T. Jessell,et al.  Midline cells and the organization of the vertebrate neuraxis. , 1993, Current opinion in genetics & development.

[17]  T. Jessell,et al.  Floor plate-derived signals and the control of neural cell pattern in vertebrates. , 1990, Harvey lectures.

[18]  P. Chesley.  Development of the short‐tailed mutant in the house mouse , 1935 .

[19]  B. Herrmann,et al.  Expression pattern of the Brachyury gene in whole-mount TWis/TWis mutant embryos. , 1991, Development.

[20]  J. Darnell,et al.  Hepatocyte nuclear factor 3/fork head or "winged helix" proteins: a family of transcription factors of diverse biologic function. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[21]  P. Good,et al.  The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos. , 1992, Genes & development.

[22]  Ken W. Y. Cho,et al.  Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid , 1991, Cell.

[23]  D. Melton,et al.  Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction. , 1987, Development.

[24]  J. Darnell,et al.  Sequential expression of HNF-3β and HNF-3α by embryonic organizing centers: the dorsal lip/node, notochord and floor plate , 1993, Mechanisms of Development.

[25]  B. Hogan,et al.  HNF-3β as a regulator of floor plate development , 1994, Cell.

[26]  O. Pourquié,et al.  Control of dorsoventral patterning of somitic derivatives by notochord and floor plate. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[27]  T. Jessell,et al.  Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons , 1988, Neuron.

[28]  H. Grüneberg.  The pathology of development : a study of inherited skeletal disorders in animals , 1963 .

[29]  T. Jessell,et al.  Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord , 1994, Cell.

[30]  M. Goulding,et al.  Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord. , 1993, Development.

[31]  J. Rossant,et al.  Anterior mesendoderm induces mouse Engrailed genes in explant cultures. , 1993, Development.

[32]  R. Bronson,et al.  Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene , 1991, Cell.

[33]  J. Darnell,et al.  Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. , 1991, Genes & development.

[34]  C. Stern,et al.  Fate mapping and cell lineage analysis of Hensen's node in the chick embryo. , 1991, Development.

[35]  C. Kintner,et al.  Cellular contacts required for neural induction in Xenopus embryos: evidence for two signals. , 1989, Development.

[36]  J. Rossant,et al.  The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. , 1993, Development.

[37]  R. Pedersen,et al.  Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. , 1991, Development.

[38]  N. Papalopulu,et al.  Xenopus Distal-less related homeobox genes are expressed in the developing forebrain and are induced by planar signals. , 1993, Development.

[39]  R. Harland,et al.  XFKH2, a Xenopus HNF-3 alpha homologue, exhibits both activin-inducible and autonomous phases of expression in early embryos. , 1993, Developmental biology.

[40]  R. Ho,et al.  The protein product of the zebrafish homologue of the mouse T gene is expressed in nuclei of the germ ring and the notochord of the early embryo. , 1992, Development.

[41]  A. R. I. Altaba,et al.  Induction and axial patterning of the neural plate: Planar and vertical signals , 1993 .

[42]  K. Flanders,et al.  Interactions between retinoids and TGF beta s in mouse morphogenesis. , 1992, Development.

[43]  R. Beddington.  Induction of a second neural axis by the mouse node. , 1994, Development.

[44]  J. Smith,et al.  Expression of a xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction , 1991, Cell.

[45]  B. Hogan,et al.  Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. , 1993, Development.

[46]  R. Balling,et al.  A role for Pax-1 as a mediator of notochordal signals during the dorsoventral specification of vertebrae. , 1993, Development.

[47]  T. Jessell,et al.  Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1. , 1992, Science.

[48]  J. Darnell,et al.  HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. , 1990, Genes & development.

[49]  R. Cortese,et al.  Cell-specific expression of a transfected human α1 -antitrypsin gene , 1985, Cell.

[50]  D. Melton,et al.  Involvement of the Xenopus homeobox gene Xhox3 in pattern formation along the anterior-posterior axis , 1989, Cell.

[51]  B. Herrmann,et al.  Immunohistochemical analysis of the Brachyury protein in wild-type and mutant mouse embryos. , 1994, Developmental biology.

[52]  M. Yaniv,et al.  Tissue‐specific expression is conferred by a sequence from the 5′ end of the rat albumin gene. , 1984, The EMBO journal.

[53]  G. von Dassow,et al.  Induction of the Xenopus organizer: expression and regulation of Xnot, a novel FGF and activin-regulated homeo box gene. , 1993, Genes & development.

[54]  V. Korzh,et al.  Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation. , 1993, Development.

[55]  G. Malacinski,et al.  Axial structure development in ultraviolet-irradiated (notochord-defective) amphibian embryos. , 1981, Developmental biology.

[56]  H. Jäckle,et al.  The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo , 1989, Cell.

[57]  P. Bovolenta,et al.  Perturbation of neuronal differentiation and axon guidance in the spinal cord of mouse embryos lacking a floor plate: analysis of Danforth's short-tail mutation. , 1991, Development.

[58]  P. Ingham,et al.  A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos , 1993, Cell.

[59]  C. Tabin,et al.  Sonic hedgehog mediates the polarizing activity of the ZPA , 1993, Cell.

[60]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[61]  A. R. I. Altaba.  Neural expression of the Xenopus homeobox gene Xhox3: evidence for a patterning neural signal that spreads through the ectoderm , 1990 .

[62]  T. Jessell,et al.  Control of cell pattern in the developing nervous system: Polarizing activity of the floor plate and notochord , 1991, Cell.

[63]  R. Ho,et al.  Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation , 1993, Cell.

[64]  Andrew P. McMahon,et al.  Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity , 1993, Cell.

[65]  C. Nüsslein-Volhard,et al.  no tail (ntl) is the zebrafish homologue of the mouse T (Brachyury) gene. , 1994, Development.

[66]  T. Jessell,et al.  Induction of floor plate differentiation by contact-dependent, homeogenetic signals. , 1993, Development.

[67]  W. Knöchel,et al.  Activin A induced expression of a fork head related gene in posterior chordamesoderm (notochord) of Xenopus laevis embryos , 1992, Mechanisms of Development.

[68]  T. Jessell,et al.  Ectopic neural expression of a floor plate marker in frog embryos injected with the midline transcription factor Pintallavis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[69]  A. R. I. Altaba.  Planar and vertical signals in the induction and patterning of the Xenopus nervous system , 1992 .

[70]  T. Jessell,et al.  Control of cell pattern in the neural tube: Motor neuron induction by diffusible factors from notochord and floor plate , 1993, Cell.

[71]  R. Costa,et al.  The restricted promoter activity of the liver transcription factor hepatocyte nuclear factor 3 beta involves a cell-specific factor and positive autoactivation , 1992, Molecular and cellular biology.

[72]  Carmen R. Domingo,et al.  Pintallavis, a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis. , 1992 .

[73]  J. Smith,et al.  Ectopic mesoderm formation in Xenopus embryos caused by widespread expression of a Brachyury homologue , 1992, Nature.

[74]  A. Poustka,et al.  Cloning of the T gene required in mesoderm formation in the mouse , 1990, Nature.

[75]  G. Crabtree,et al.  Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters. , 1987, Science.

[76]  W. Rutter,et al.  Cell-specific expression controlled by the 5′-flanking region of insulin and chymotrypsin genes , 1983, Nature.

[77]  Mario R. Capecchi,et al.  Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes , 1988, Nature.

[78]  K. Kaestner,et al.  Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. , 1993, Development.

[79]  R. Toyama,et al.  Expression patterns of the murine LIM class homeobox gene lim1 in the developing brain and excretory system , 1994, Developmental dynamics : an official publication of the American Association of Anatomists.

[80]  M. Monk,et al.  HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells , 1987, Nature.