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Updated: Feb 11, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
Atrioventricular canal defect and genetic syndromes: The unifying role of sonic hedgehog
M C Digilio1, F Pugnaloni2, A De Luca3
1Medical Genetics, Pediatric Cardiology, Genetics and Rare Diseases Research Division, Bambino Gesù Pediatric Hospital, Rome, Italy.
Insights
Atrioventricular canal defects (AVCD), a common congenital heart defect, may be linked to Hedgehog (Hh) signaling pathway disruptions. This review explores Hh signaling
Area of Science:
- Developmental Biology
- Cardiovascular Science
- Genetics
Background:
- Atrioventricular canal defect (AVCD) is a frequent congenital heart defect (CHD), often accompanied by extracardiac anomalies.
- AVCD in certain polydactyly syndromes shares features with heterotaxy, a condition linked to cilia dysfunction and aberrant Hedgehog (Hh) signaling.
- Hedgehog signaling is crucial for left-right body asymmetry and cardiovascular development, particularly the secondary heart field (SHF).
Purpose of the Study:
- To review the potential role of Hedgehog (Hh) signaling in the pathogenesis of atrioventricular canal defects (AVCD).
- To explore how Hh pathway perturbations may lead to overlapping developmental errors with AVCD as a common finding.
- To consider AVCD within the framework of "developmental fields" affected by genetic and environmental factors.
Main Methods:
- Literature review synthesizing observations on AVCD, polydactyly syndromes, heterotaxy, and Hh signaling.
- Analysis of experimental data on Hh pathway components and their impact on cardiovascular development.
- Conceptual review applying the "developmental field" concept to malformations.
Main Results:
- Perturbations in various Hh pathway components can result in developmental abnormalities, frequently including AVCD.
- The cardiac phenotype in some AVCD-associated syndromes resembles that seen in heterotaxy, implicating Hh signaling.
- The secondary heart field (SHF), vital for AVCD formation, is influenced by Hh signaling at the venous pole.
Conclusions:
- Hedgehog (Hh) signaling is a potential key player in the pathogenesis of atrioventricular canal defects (AVCD) across various genetic disorders.
- AVCD can be conceptualized as a defect within a broader "developmental field," susceptible to disruption by genetic and environmental factors.
- Understanding Hh pathway involvement offers insights into the complex etiology of congenital heart defects like AVCD.
Abstract:
The atrioventricular canal defect (AVCD) is a congenital heart defect (CHD) frequently associated with extracardiac anomalies (75%). Previous observations from a personal series of patients with AVCD and "polydactyly syndromes" showed that the distinct morphology and combination of AVCD features in some of these syndromes is reminiscent of the cardiac phenotype found in heterotaxy, a malformation complex previously associated with functional cilia abnormalities and aberrant Hedgehog (Hh) signaling. Hh signaling coordinates multiple aspects of left-right lateralization and cardiovascular growth. Being active at the venous pole the secondary heart field (SHF) is essential for normal development of dorsal mesenchymal protrusion and AVCD formation and septation. Experimental data show that perturbations of different components of the Hh pathway can lead to developmental errors presenting with partially overlapping manifestations and AVCD as a common denominator. We review the potential role of Hh signaling in the pathogenesis of AVCD in different genetic disorders. AVCD can be viewed as part of a "developmental field," according to the concept that malformations can be due to defects in signal transduction cascades or pathways, as morphogenetic units which may be altered by Mendelian mutations, aneuploidies, and environmental causes.
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