Related Experiment Video

Updated: Jul 4, 2026

Studying Wnt Signaling During Patterning of Conducting Airways

Studying Wnt Signaling During Patterning of Conducting Airways

Published on: October 16, 2016

Unique spatial and cellular expression patterns of Hoxa5, Hoxb4, and Hoxb6 proteins in normal developing murine lung

MaryAnn Vitoria Volpe¹, Karen Ting Wai Wang, Heber Carl Nielsen

¹Div. of Newborn Medicine, Department of Pediatrics, Tufts Medical Center, Boston, Massachusetts 02111, USA. mvolpe1@tuftsmedicalcenter.org

Birth Defects Research. Part A, Clinical and Molecular Teratology

|June 17, 2008

Abstract

Background:

Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial, and cellular expression of Hoxa5, Hoxb4, and Hoxb6 proteins compared to normal lung development.

Methods:

Temporal, spatial, and cellular Hoxa5, Hoxb4, and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, and 19 fetuses and neonates using Western blot and immunohistochemistry.

Results:

Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 protein isoforms changed with development and were altered further in NT-PH lungs. Compared to normal lungs, GD19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways.

Conclusions:

Unique spatial and cellular expression of Hoxa5, Hoxb4, and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition.

More Related Videos

Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis

Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis

Published on: January 4, 2017

Generation of 3D Whole Lung Organoids from Induced Pluripotent Stem Cells for Modeling Lung Developmental Biology and Disease

Generation of 3D Whole Lung Organoids from Induced Pluripotent Stem Cells for Modeling Lung Developmental Biology and Disease

Published on: April 12, 2021

Related Concept Videos

Hedgehog Signaling Pathway

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

Pleiotropy

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...

Articles linked to this work by shared authors, journal, and citation graph.

Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011.

Birth defects research. Part A, Clinical and molecular teratology·2016

Evaluation of the Western Australian Register of Developmental Anomalies: Thirty-five years of surveillance.

Birth defects research. Part A, Clinical and molecular teratology·2016

A quality assessment of reporting sources for microcephaly in Utah, 2003 to 2013.

Birth defects research. Part A, Clinical and molecular teratology·2016

Editorial brain malformation surveillance in the Zika era.

Birth defects research. Part A, Clinical and molecular teratology·2016

Characterizing facial features in individuals with craniofacial microsomia: A systematic approach for clinical research.

Birth defects research. Part A, Clinical and molecular teratology·2016

Population-based microcephaly surveillance in the United States, 2009 to 2013: An analysis of potential sources of variation.

Birth defects research. Part A, Clinical and molecular teratology·2016

See all related articles