Nkx2.5 and Nkx2.6, homologs of Drosophila tinman, are required for development of the pharynx.
Nkx2.5 and Nkx2.6 are murine homologs of Drosophila tinman. Their genes are expressed in the ventral region of the pharynx at early stages of embryogenesis. However, no abnormalities in the pharynges of embryos with mutations in either Nkx2.5 or Nkx2.6 have been reported. To examine the function of Nkx2.5 and Nkx2.6 in the formation of the pharynx, we generated and analyzed Nkx2.5 and Nkx2.6 double-mutant mice. Interestingly, in the double-mutant embryos, the pharynx did not form properly. Pharyngeal endodermal cells were largely missing, and the mutant pharynx was markedly dilated. Moreover, we observed enhanced apoptosis and reduced proliferation in pharyngeal endodermal cells of the double-mutant embryos. These results demonstrated a critical role of the NK-2 homeobox genes in the differentiation, proliferation, and survival of pharyngeal endodermal cells. Furthermore, the development of the atrium was less advanced in the double-mutant embryos, indicating that these two genes are essential for both pharyngeal and cardiac development.
Tanaka
M
M
Cardiovascular Division, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Schinke
M
M
Liao
H S
HS
Yamasaki
N
N
Izumo
S
S
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D005314:Embryonic and Fetal Development; D004707:Endoderm / Q000166:cytology; D015870:Gene Expression; D005801:Genes, Homeobox; D006321:Heart / Q000196:embryology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D010614:Pharynx / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D010641:Phenotype; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors; D029867:Xenopus Proteins
D029721:Drosophila Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; C111285:Nkx2-6 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; C102933:tin protein, Drosophila