Expression of Hoxb-5 during human lung development and in congenital lung malformations.
BACKGROUND
We have previously shown that the Hox gene Hoxb-5 is necessary for normal mouse lung branching morphogenesis. Abnormal Hoxb-5 regulation causes specific alterations in airway branching. We hypothesized that Hoxb-5 is similarly involved in human lung branching morphogenesis, and is abnormally expressed in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), both of which are congenital lung malformations with abnormal airway development.


METHODS
The temporal, spatial, and cellular expression of the Hoxb-5 protein was evaluated in normal human lung and BPS and CCAM tissue using Western blot analysis and immunocytochemistry.


RESULTS
The expression of Hoxb-5 during human lung development showed strong similarities to that during mouse lung development. Western blots showed high Hoxb-5 protein levels in the pseudoglandular period (PSG), decreased but sustained levels in the canalicular period (CAN), and negligible levels during the alveolar period (ALV). Immunocytochemistry showed Hoxb-5 protein expression in mesenchymal cells around branching airways in the pseuodglandular period, subepithelial fibroblast localization (especially at airway branch points) in the CAN and minimal expression in the ALV. In BPS and CCAM tissue, Hoxb-5 protein levels were increased compared to age- and developmentally-matched lung tissue, and were more similar to the PSG and CAN with Hoxb-5-positive cells in mesenchyme surrounding abnormally branched airways.


CONCLUSIONS
Hoxb-5 expression during human lung branching morphogenesis, which is similar to that observed in mouse lung development, indicates that it plays a role in controlling airway patterning. This notion is supported by results from BPS and CCAM tissue, in which Hoxb-5 is maintained in a manner typical of an earlier developmental stage and is associated with development of abnormal lung tissue.
Volpe
MaryAnn V
MV
Department of Pediatrics, Division of Newborn Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. mvolpe1@tufts-nemc.org
Pham
Lucia
L
Lessin
Marc
M
Ralston
Steven J
SJ
Bhan
Ina
I
Cutz
Ernest
E
Nielsen
Heber C
HC
D001998:Bronchopulmonary Sequestration / Q000378:metabolism* / Q000473:pathology; D002675:Child, Preschool; D015615:Cystic Adenomatoid Malformation of Lung, Congenital / Q000378:metabolism* / Q000473:pathology; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D009024:Morphogenesis; D011650:Pulmonary Alveoli / Q000196:embryology
C489126:HOXB5 protein, human; D018398:Homeodomain Proteins