Chicken Nkx-2.8: a novel homeobox gene expressed in early heart progenitor cells and pharyngeal pouch-2 and -3 endoderm.

Members of the NK family of homeobox transcription factors regulate critical steps of organogenesis during vertebrate development. In the studies described in this report, we have isolated and functionally characterized the chicken Nkx-2.8 (cNkx-2.8) cDNA and protein and defined the temporal and spatial pattern of cNkx-2.8 gene expression during chicken development. cNkx-2.8 transcripts are first detectable at HH stage 7 in the splanchnopleura. At stage 10(+), the cNkx-2.8 gene is expressed in the linear heart tube and the dorsal half of the vitelline vein. However, after looping, HH stage 13, cNkx-2.8 is no longer expressed in the looped heart tube, but is expressed in the ventral pharyngeal endoderm. At stage 15, in addition to the pharyngeal expression pattern, cNkx-2.8 is expressed in the ectoderm of the pharyngeal arches and the aortic sac. By HH Stage 17, cNkx-2.8 expression is detectable in lateral endoderm of the second and third pharyngeal pouches, the posterior portion of the aortic sac, and the sinus venosus. cNkx-2.8 binds to previously characterized Nkx2-1 and Nkx2-5 DNA-binding sites and overexpression of cNkx-2.8 transactivates a minimal promoter which contains multimerized Nkx-2 DNA-binding sites. In addition, cNkx-2.8 and serum response factor can coactivate a minimal cardiac alpha-actin promoter. These data are consistent with a model in which cNkx-2.8 performs a unique temporally and spatially restricted function in the developing embryonic heart and pharyngeal region. Moreover, the coexpression of cNkx-2.5 and -2.8 raises the possibility that cNkx-2. 8 may have a redundant role with cNkx-2.5 in the coalescing heart tube and may play an important role in the transcriptional program(s) that underlies thymus formation. The existence of multiple NK-2 family members and their partially overlapping patterns of expression are discussed within the framework of a "Nkx code."

[1]  Chaya Kalcheim,et al.  The Neural Crest: Author Index , 1999 .

[2]  M. Kirby,et al.  Abnormal patterning of the aortic arch arteries does not evoke cardiac malformations , 1997, Developmental dynamics : an official publication of the American Association of Anatomists.

[3]  Kyu-Ho Lee,et al.  A new tinman-related gene, nkx2.7, anticipates the expression of nkx2.5 and nkx2.3 in zebrafish heart and pharyngeal endoderm. , 1996, Developmental biology.

[4]  M. Fishman,et al.  Zebrafish tinman homolog demarcates the heart field and initiates myocardial differentiation. , 1996, Development.

[5]  R. Schwartz,et al.  Recruitment of the tinman homolog Nkx-2.5 by serum response factor activates cardiac alpha-actin gene transcription , 1996, Molecular and cellular biology.

[6]  J. B. Jaynes,et al.  A conserved region of engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo. , 1996, Development.

[7]  R. Harvey.  NK-2 homeobox genes and heart development. , 1996, Developmental biology.

[8]  R. Gibbs,et al.  Improved ligation-anchored PCR strategy for identification of 5' ends of transcripts. , 1996, BioTechniques.

[9]  R. Schwartz,et al.  Transcriptional regulation of a mouse Clara cell-specific protein (mCC10) gene by the NKx transcription factor family members thyroid transciption factor 1 and cardiac muscle-specific homeobox protein (CSX) , 1996, Molecular and cellular biology.

[10]  H. Arnold,et al.  Chick NKx-2.3 represents a novel family member of vertebrate homologues to the Drosophila homeo☐ gene tinman: differential expression of cNKx-2.3 and cNKx-2.5 during heart and gut development , 1996, Mechanisms of Development.

[11]  M. Kessel,et al.  Checklist: Vertebrate homeo☐ genes , 1996, Mechanisms of Development.

[12]  R. Schwartz,et al.  Activation of the cardiac alpha-actin promoter depends upon serum response factor, Tinman homologue, Nkx-2.5, and intact serum response elements. , 1996, Developmental genetics.

[13]  C H Fox,et al.  The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. , 1996, Genes & development.

[14]  A. Lassar,et al.  Induction of avian cardiac myogenesis by anterior endoderm. , 1995, Development.

[15]  M. Rudnicki,et al.  Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis. , 1995, Developmental biology.

[16]  N. Papalopulu,et al.  tinman, a Drosophila homeobox gene required for heart and visceral mesoderm specification, may be represented by a family of genes in vertebrates: XNkx-2.3, a second vertebrate homologue of tinman. , 1995, Development.

[17]  L. Velasco,et al.  vnd, a gene required for early neurogenesis of Drosophila, encodes a homeodomain protein. , 1995, The EMBO journal.

[18]  S. Dremier,et al.  Study of TTF-1 gene expression in dog thyrocytes in primary culture , 1995, Molecular and Cellular Endocrinology.

[19]  Ruili Li,et al.  Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. , 1995, Genes & development.

[20]  M. Capecchi,et al.  The role of Hoxa-3 in mouse thymus and thyroid development. , 1995, Development.

[21]  R J Schwartz,et al.  Identification of Novel DNA Binding Targets and Regulatory Domains of a Murine Tinman Homeodomain Factor, nkx-2.5(*) , 1995, The Journal of Biological Chemistry.

[22]  S. Wilson,et al.  Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain. , 1995, Development.

[23]  A. Saiardi,et al.  Cloning and sequence analysis of human thyroid transcription factor 1. , 1995, Biochimica et biophysica acta.

[24]  R. Lauro,et al.  The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis , 1994, Molecular and cellular biology.

[25]  S. Formisano,et al.  Sequence-specific DNA recognition by the thyroid transcription factor-1 homeodomain. , 1994, Nucleic acids research.

[26]  R. Ivarie,et al.  Polyvinyl alcohol enhances detection of low abundance transcripts in early stage quail embryos in a nonradioactive whole mount in situ hybridization technique. , 1994, BioTechniques.

[27]  A. Fire,et al.  The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle. , 1994, Development.

[28]  E. Boncinelli,et al.  The thyroid transcription factor‐1 gene is a candidate target for regulation by Hox proteins. , 1994, The EMBO journal.

[29]  T. Lints,et al.  XNkx-2.5, a Xenopus gene related to Nkx-2.5 and tinman: evidence for a conserved role in cardiac development. , 1994, Developmental biology.

[30]  L Hartley,et al.  Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. , 1993, Development.

[31]  I. Komuro,et al.  Csx: a murine homeobox-containing gene specifically expressed in the developing heart. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Frasch,et al.  tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. , 1993, Genes & development.

[33]  R. Bodmer.  The gene tinman is required for specification of the heart and visceral muscles in Drosophila. , 1993, Development.

[34]  M. Shankland,et al.  Lox10, a member of the NK-2 homeobox gene class, is expressed in a segmental pattern in the endoderm and in the cephalic nervous system of the leech Helobdella. , 1993, Development.

[35]  M. Saha,et al.  A Xenopus homebox gene defines dorsal-ventral domains in the developing brain. , 1993, Development.

[36]  H. Francis-Lang,et al.  Functional role of TTF‐1 binding sites in bovine thyroglobulin promoter , 1992, FEBS letters.

[37]  R. Krumlauf.  Evolution of the vertebrate Hox homeobox genes , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[38]  D. Duboule,et al.  Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain , 1992, Neuron.

[39]  R. Krumlauf,et al.  Hox codes and positional specification in vertebrate embryonic axes. , 1992, Annual review of cell biology.

[40]  R. Lauro,et al.  The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. , 1991, Development.

[41]  Peter Gruss,et al.  Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid , 1991, Cell.

[42]  F. Gonzalez,et al.  thyroid transcription factor TTF-1 . characterization , and structural identity with ( T / EBP ) : cDNA cloning , functional Thyroid-specific enhancer-binding protein , 1991 .

[43]  J. Garcia-Fernández,et al.  Planarian homeobox genes: cloning, sequence analysis, and expression. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[44]  G. Damante,et al.  Several regions of Antennapedia and thyroid transcription factor 1 homeodomains contribute to DNA binding specificity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[45]  M. Capecchi,et al.  Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5 , 1991, Nature.

[46]  M. Mattéi,et al.  Thyroid nuclear factor 1 (TTF‐1) contains a homeodomain and displays a novel DNA binding specificity. , 1990, The EMBO journal.

[47]  Y. Jan,et al.  A new homeobox-containing gene, msh-2, is transiently expressed early during mesoderm formation of Drosophila. , 1990, Development.

[48]  R. Koski,et al.  Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals , 1990, Molecular and cellular biology.

[49]  M. Kirby,et al.  Alteration of early vascular development after ablation of cranial neural crest , 1989, The Anatomical Record.

[50]  M. Nirenberg,et al.  Drosophila NK-homeobox genes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[51]  D. Lockshon,et al.  MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer , 1989, Cell.

[52]  R. Lauro,et al.  A thyroid‐specific nuclear protein essential for tissue‐specific expression of the thyroglobulin promoter. , 1989, The EMBO journal.

[53]  R. Krumlauf,et al.  Mouse homeo-genes within a subfamily, Hox-1.4, -2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage- and tissue-dependent differences in their regulation. , 1989, Development.

[54]  M. Kirby.  Plasticity and predetermination of mesencephalic and trunk neural crest transplanted into the region of the cardiac neural crest. , 1989, Developmental biology.

[55]  M. Scott,et al.  The structure and function of the homeodomain. , 1989, Biochimica et biophysica acta.

[56]  S. Gaunt.  Mouse homeobox gene transcripts occupy different but overlapping domains in embryonic germ layers and organs: a comparison of Hox-3.1 and Hox-1.5. , 1988, Development.

[57]  J. B. Armstrong,et al.  Differentiation of cartilage from cranial neural crest in the axolotl (Ambystoma mexicanum). , 1987, Differentiation; research in biological diversity.

[58]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[59]  M. Kirby,et al.  Characterization of conotruncal malformations following ablation of “cardiac” neural crest , 1985, The Anatomical record.

[60]  G. Church,et al.  Genomic sequencing. , 1993, Methods in molecular biology.

[61]  J. Bee,et al.  The role of tissue interactions in the skeletogenic differentiation of avian neural crest cells. , 1980, Developmental biology.

[62]  H. Epperlein.  The ectomesenchymal-endodermal interaction-system (EEIS) of Triturus alpestris in tissue culture. I. Observations on attachment, migration and differentiation of neural crest cells. , 1974, Differentiation; research in biological diversity.

[63]  S. Hörstadius.  The neural crest : its properties and derivatives in the light of experimental research , 1950 .