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Development of the Interventricular Septum

Sources: The Developing Human: Clinically Oriented Embryology (Moore et al.) & Langman's Medical Embryology

Overview

The interventricular septum (IVS) divides the single primordial ventricle into the right and left ventricles. Its formation is one of the most complex partitioning events in cardiac embryology because it involves contributions from three distinct tissue sources and must be perfectly coordinated with outflow tract septation. Errors in this process produce ventricular septal defects (VSDs) - the most common congenital heart defect.

Stage 1: Appearance of the Primordial Ventricle (Week 4)

By the end of the 4th week, the primitive heart tube consists of several segments: the sinus venosus, atrium, atrioventricular canal, ventricle, bulbus cordis, and truncus arteriosus.

The primordial single ventricle begins to expand. As the two sides balloon outward (the left and right primitive ventricles), their medial walls become apposed and gradually merge at the floor of the ventricle, near the apex. This merging creates the first sign of the IVS.

Fig 13.18A - Primordial heart at 5 weeks showing bulbus cordis, ventricles, and the primordial interventricular septum forming at the apex

Fig 13.18A-B: Left - Sagittal section at 5 weeks showing the primitive heart chambers including the primordial IVS. Right - At 6 weeks after the bulbus cordis is incorporated, showing the growing muscular IVS, interventricular groove, and aortic vestibule. (The Developing Human)

Stage 2: Formation of the Muscular Interventricular Septum (Weeks 4-6)

A median ridge - the muscular interventricular septum - rises from the floor of the ventricle near its apex. Key features:

Myocytes from both the left and right primordial ventricles contribute to it
The septum has a concave free (superior) edge, leaving a gap called the interventricular foramen
Initially the septum grows primarily because the ventricles on either side dilate outward (passive growth)
Later, active proliferation of myoblasts within the septum increases its size

Fig 13.17A-B: Muscular IVS development with interventricular foramen, fused endocardial cushions, and blood flow directions

Fig 13.17A-B: A - Sagittal section late in the 5th week showing the muscular IVS with its concave free edge and the interventricular foramen above it. B - Coronal section at a slightly later stage showing blood flow directions (blue arrows) and ventricle expansion (black arrows). (The Developing Human)

Stage 3: The Interventricular Foramen (Weeks 5-7)

Until the 7th week, a crescent-shaped interventricular foramen (IVF) sits between:

The free (superior/concave) edge of the muscular IVS
The fused endocardial cushions

This foramen allows right-left ventricular communication during development. It must be closed to complete cardiac septation.

Fig 13.19A-B: Internal coronal view showing the developing IVS with valve swellings, interventricular foramen, and early muscular septum

Fig 13.19A-B: A (left) - At ~5-6 weeks, showing the muscular IVS with valve swellings and left AV canal. B (right) - Later stage showing the IVS enlarging, with the foramen still open above it. (The Developing Human)

Stage 4: Closure of the Interventricular Foramen and Formation of the Membranous IVS (Week 7)

This is the most intricate step. The IVF closes by the end of the 7th week through fusion of tissue from three sources:

Source	Contribution
Right bulbar ridge	Contributes to the membranous IVS from the right side
Left bulbar ridge	Contributes to the membranous IVS from the left side
Endocardial cushion	Subendocardial tissue extends from the right side of the endocardial cushion downward along the top of the muscular IVS

These three tissues merge with each other and with the aorticopulmonary septum, completing the membranous part of the IVS.

Fig 13.18C showing bulbar ridges, the interventricular foramen, fused endocardial cushions, and free edge of muscular IVS at 6 weeks

Fig 13.18C-D: C - At 6 weeks, the right and left bulbar ridges (yellow and tan) and endocardial cushion (blue) are visible converging at the interventricular foramen. D - Slightly later: right and left atrioventricular canals now separated. (The Developing Human)

Fig 13.18E showing the completed membranous IVS formed from the three tissue sources (color coded)

Fig 13.18E: The completed interventricular septum. The membranous part (upper) is formed by fusion of the right bulbar ridge (tan), left bulbar ridge (yellow), and endocardial cushion (blue). The muscular part forms the bulk of the septum below. (The Developing Human)

The Final IVS: Two Parts

After closure is complete, the IVS has two distinct regions:

1. Muscular Part (larger, inferior)

Thick, myocardium-rich
Formed by fusion of the medial walls of the expanding left and right ventricles
Has trabeculations on its surfaces

2. Membranous Part (smaller, superior)

Thin, fibrous, located in the upper-posterior IVS
Derived from fusion of: right bulbar ridge + left bulbar ridge + endocardial cushion tissue + neural crest cells
The most common site of ventricular septal defects

Fig 13.19C-D: Heart at 7 weeks (C) showing the membranous and muscular parts of the completed IVS, developing mitral valve, trabeculae carneae; and at 20 weeks (D) with conduction system

Fig 13.19C-D: C - At 7 weeks: the completed IVS with membranous and muscular parts labeled, plus developing mitral valve and trabeculae carneae. D - At 20 weeks: the mature ventricular structure with the AV bundle running through the membranous IVS. (The Developing Human)

Langman's View: 7th-Week Cross-Section

Langman's Fig 13.29 - Frontal section at end of 7th week showing completed conus septum, muscular IVS, right and left ventricular outflow channels

Langman's Fig 13.29: Frontal section through the heart at end of the 7th week. The conus septum (yellow) is complete above the muscular IVS. Left ventricular blood now flows into the aorta; right ventricular blood into the pulmonary trunk. The oval foramen and muscular IVS are clearly visible. (Langman's Medical Embryology)

Langman's Fig 13.28 - 3D view of the 7th week heart showing the conus septum, muscular IVS, outflow tracts, moderator band

Langman's Fig 13.28: 3D frontal section at the 7th week showing the muscular interventricular septum at the base, conus septum above, pulmonary valves, right and left outflow tracts, moderator band, and tricuspid orifice. (Langman's Medical Embryology)

Summary Timeline

Week	Event
Week 4	Primordial ventricle expands; medial walls begin merging → primordial muscular IVS appears at the apex
Weeks 4-6	Muscular IVS grows upward; interventricular foramen remains open (crescent-shaped gap)
Week 6	Bulbar ridges begin fusing; endocardial cushion tissue starts extending toward the IVS
Week 7	IVF closes completely; membranous IVS formed from right bulbar ridge + left bulbar ridge + endocardial cushion; aorta and pulmonary trunk now connected to separate ventricles

Clinical Correlation: Ventricular Septal Defects (VSDs)

VSDs are the most common congenital heart defect, accounting for ~25% of all CHDs.

Type	Cause	Frequency
Membranous VSD	Failure of subendocardial tissue extension from endocardial cushion to fuse with the aorticopulmonary septum and muscular IVS	Most common (~80%)
Muscular VSD	Excessive cavitation of myocardial tissue during ventricular wall formation; can produce multiple small holes ("Swiss cheese" septum)	Less common
Single ventricle (cor triloculare)	Complete failure of IVS formation	Extremely rare

Small VSDs (30-50%) close spontaneously in the first year of life. Large VSDs cause left-to-right shunting, increased pulmonary blood flow, pulmonary hypertension, dyspnea, and early cardiac failure.

Key memory point: The membranous IVS is the product of three-way fusion - right bulbar ridge + left bulbar ridge + endocardial cushion. Failure of any one of these to meet properly leaves a membranous VSD. - The Developing Human, p. 813-815; Langman's Medical Embryology, p. 219-220

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