Programmed cell death along the midline axis patterns ipsilaterality in gastrulation

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Science  10 Jan 2020:
Vol. 367, Issue 6474, pp. 197-200
DOI: 10.1126/science.aaw2731

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Apoptosis prevents left-right crossing

Animals generally display a bilateral body plan, with symmetry between the left and right sides. Maya-Ramos and Mikawa examined the mechanism that prevents the crossing of cells between sides. Using chick embryos, they show that cellular mixing between sides is prevented by a barrier at the embryonic midline that involves programmed cell death and the extracellular matrix. This work demonstrates the dependence of normal development on programmed cell death during the gastrulation stage.

Science, this issue p. 197


Bilateral symmetry is the predominant body plan in the animal kingdom. Cells on the left and right sides remain compartmentalized on their ipsilateral side throughout life, but with occasional variation, as evidenced by gynandromorphs and human disorders. How this evolutionarily conserved body plan is programmed remains a fundamental yet unanswered question. Here, we show that germ-layer patterning in avian gastrulation is ipsilateral despite cells undergoing highly invasive mesenchymal transformation and cell migration. Contralateral invasion is suppressed by extracellular matrix (ECM) and programmed cell death (PCD) along the embryonic midline. Ipsilateral gastrulation was lost by midline ECM and PCD inhibition but restored with exogenously induced PCD. Our data support ipsilaterality as an integral component of bilaterality and highlight a positive functional role of PCD in development.

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