RGD Reference Report - Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development.

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Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development.
Authors:	Roux, M Laforest, B Capecchi, M Bertrand, N Zaffran, S
Citation:	Roux M, etal., Dev Biol. 2015 Oct 15;406(2):247-58. doi: 10.1016/j.ydbio.2015.08.015. Epub 2015 Aug 15.
RGD ID:	11052805
Pubmed:	PMID:26284287 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.ydbio.2015.08.015 (Journal Full-text)
Outflow tract (OFT) anomalies are among the most common congenital heart defects found at birth. The embryonic OFT grows by the progressive addition of cardiac progenitors, termed the second heart field (SHF), which originate from splanchnic pharyngeal mesoderm. Development of the SHF is controlled by multiple intercellular signals and transcription factors; however the relationship between different SHF regulators remains unclear. We have recently shown that Hoxa1 and Hoxb1 are expressed in a sub-population of the SHF contributing to the OFT. Here, we report that Hoxb1 deficiency results in a shorter OFT and ventricular septal defects (VSD). Mechanistically, we show that both FGF/ERK and BMP/SMAD signaling, which regulate proliferation and differentiation of cardiac progenitor cells and OFT morphogenesis, are enhanced in the pharyngeal region in Hoxb1 mutants. Absence of Hoxb1 also perturbed SHF development through premature myocardial differentiation. Hence, the positioning and remodeling of the mutant OFT is disrupted. Hoxa1(-/-) embryos, in contrast, have low percentage of VSD and normal SHF development. However, compound Hoxa1(-/-); Hoxb1(+/-) embryos display OFT defects associated with premature SHF differentiation, demonstrating redundant roles of these factors during OFT development. Our findings provide new insights into the gene regulatory network controlling SHF and OFT formation.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
HOXB1	Human	Ventricular Outflow Obstruction		ISO	Hoxb1 (Mus musculus)		RGD
Hoxb1	Rat	Ventricular Outflow Obstruction		ISO	Hoxb1 (Mus musculus)		RGD
Hoxb1	Mouse	Ventricular Outflow Obstruction		IMP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Hoxb1 (homeo box B1)

Genes (Mus musculus)

Hoxb1 (homeobox B1)

Genes (Homo sapiens)

HOXB1 (homeobox B1)

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Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development.