Distinct roles of HF-1b/Sp4 in ventricular and neural crest cells lineages affect cardiac conduction system development.
The heterogeneous cell types of the cardiac conduction system are responsible for coordinating and maintaining rhythmic contractions of the heart. While it has been shown that the cells of the conduction system are derived from myocytes, additional cell types, including neural crest cells, may play a role in the development and maturation of these specialized cell lineages. Previous work has shown that the expression of the hf-1b gene is required for specification of the cardiac conduction system. Using Cre-Lox technology, we conditionally mutated the hf-1b gene in the ventricular and the neural crest cell lineages. Cx40 immunohistochemistry on HF-1b tissue-restricted knockouts revealed a requirement for HF-1b in the cardiomyogenic lineage. Electrophysiological studies identified a second requirement for HF-1b in the neural crest-derived cells. Absence of HF-1b in the neural crest led to atrial and atrioventricular dysfunction resulting from deficiencies in the neurotrophin receptor trkC. Therefore, in this study, we document that a single transcription factor, HF-1b, acts through two separate cell types to direct distinct functions of the cardiac conduction system.
St Amand
Tara R
TR
Institute of Molecular Medicine, University of California, San Diego, La Jolla, CA 92092, USA.
Lu
Jonathan T
JT
Zamora
Monica
M
Gu
Yusu
Y
Stricker
Janelle
J
Hoshijima
Masahiko
M
Epstein
Jonathan A
JA
Ross
John J
JJ
Ruiz-Lozano
Pilar
P
Chien
Kenneth R
KR
D000818:Animals; D001283:Atrioventricular Node / Q000294:innervation; D019070:Cell Lineage; D017630:Connexins / Q000032:analysis; D006329:Heart Conduction System / Q000196:embryology*; D006352:Heart Ventricles / Q000166:cytology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000502:physiology; D009432:Neural Crest / Q000166:cytology*; D010641:Phenotype; D020812:Receptor, trkC / Q000502:physiology; D051706:Sp4 Transcription Factor / Q000502:physiology*; D000097003:Gap Junction alpha-5 Protein
D017630:Connexins; D020812:Receptor, trkC; D051706:Sp4 Transcription Factor; D000097003:Gap Junction alpha-5 Protein; C497125:Sp4 protein, mouse