The mouse forkhead gene Foxp2 modulates expression of the lung genes.
OBJECTIVE
Foxp2 is expressed in the lung during mouse development. A monoclonal anti-mouse Foxp2 antibody was created to determine the expression pattern in the developing lung. Next, transcriptional control of two lung genes, CC10 and surfactant protein C (SPC) genes, by Foxp2 was investigated in H441 and A549 cells. Thirdly, expression patterns of Foxp2 and Foxf2 were compared in the developing lung. Finally, Foxp2 expression was determined in the Foxf2-null mice.


METHODS
Immunohistochemical staining and in situ hybridization were applied to the sections of lungs in the developing embryos.


RESULTS
Monoclonal anti-Foxp2 antibody demonstrated that Foxp2 was expressed in the bronchial epithelium at E10.5 and its expression became restricted to the distal portion of the elongating bronchiolar epithelium and finally to type II alveolar epithelial cells around birth and in the adult. Foxp2 activated the SPC gene promoter in the presence of Nkx2.1 in A549 cells while it repressed the CC10 gene promoter in H441 cells. Next, the expression domains of the Foxp2 and Foxf2 were found to be exclusive in the lung. Finally, the expression of Foxp2 did not change in the lung of Foxf2-null mice.


CONCLUSIONS
The Foxp2 protein is expressed in the growing distal edge of airway epithelium. When the bronchiolus elongates, Foxp2 suppresses CC10 expression. When the lung alveolus is formed, Foxp2 modulates the Nkx2.1-mediated SPC expression in type II alveolar cells. Foxp2 and Foxf2 independently play distinct roles in the alveoli and the mesenchyme, respectively.
Yang
Zhi
Z
Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu, Japan.
Hikosaka
Keisuke
K
Sharkar
Mohammad T K
MT
Tamakoshi
Tomoki
T
Chandra
Abhishek
A
Wang
Bo
B
Itakura
Tatsuo
T
Xue
XiaoDong
X
Uezato
Tadayoshi
T
Kimura
Wataru
W
Miura
Naoyuki
N
D000818:Animals; D000911:Antibodies, Monoclonal; D001980:Bronchi / Q000196:embryology / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008819:Mice, Nude; D011650:Pulmonary Alveoli / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014598:Uteroglobin / Q000235:genetics* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C486412:Foxf2 protein, mouse; C432918:Foxp2 protein, mouse; D037721:Pulmonary Surfactant-Associated Protein C; D012097:Repressor Proteins; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin