Circulatory System

Circulatory System Development

The heart develops from splanchnic mesoderm, beating by day 21. The primitive heart tube undergoes an astonishingly complex sequence of looping, septation, and remodeling to form the adult four-chambered heart.

Days 16–21 — PHF & SHF — Heart Tube Formation

Week 3 — Heart Fields & Vessel Formation

The vascular system appears mid-third week. Week 3: Cardiac tube forms; primordia fuse. Weeks 4–7: Chamber formation, septation, valve development. Weeks 8–20: Vascular remodeling. Late gestation: transition to neonatal circulation.
Primary Heart Field (PHF): Progenitor cells migrate from epiblast days 16–18 into splanchnic mesoderm, forming a horseshoe cluster. Fate: atria, left ventricle, part of right ventricle.
Secondary Heart Field (SHF): Cells medial to the cardiac crescent lengthen the outflow tract. Derivatives: Right Ventricle, Conus Cordis, Truncus Arteriosus. Failure leads to DORV and VSDs.
Serotonin Signaling (5-HT): drives PITX2 expression for left-sided programming. Disruption causes Dextrocardia, Heterotaxy, and VSDs. SSRIs have teratogenic effects on 5-HT signaling.
Vasculogenesis: De novo vessel formation. FGF2 induces hemangioblasts. VEGF drives coalescence into a primary vascular network.
Angiogenesis: Sprouting of new vessels from existing ones, also regulated by VEGF.