A chemo-mechanical model of endoderm movements driving elongation of the amniote hindgut

While mechanical and biochemical descriptions of development are each essential, integration of upstream morphogenic cues with downstream tissue mechanics remains understudied in many contexts during vertebrate morphogenesis. A posterior gradient of Fibroblast Growth Factor (FGF) ligands generates a contractile force gradient in the definitive endoderm, driving collective cell movements to form the hindgut. Here, we developed a two-dimensional chemo-mechanical model to investigate how mechanical properties of the endoderm and transport properties of FGF coordinately regulate this process. We began by formulating a 2-D reaction-diffusion-advection model that describes the formation of an FGF protein gradient due to posterior displacement of cells transcribing unstable Fgf8 mRNA during axis elongation, coupled with translation, diffusion, and degradation of FGF protein. This was used together with experimental measurements of FGF activity in the chick endoderm to inform a continuum model of definitive endoderm as an active viscous fluid that generates contractile stresses in proportion to FGF concentration. The model replicated key aspects of hindgut morphogenesis, confirms that heterogeneous - but isotropic - contraction is sufficient to generate large anisotropic cell movements, and provides new insight into how chemomechanical coupling across the mesoderm and endoderm coordinates hindgut elongation with outgrowth of the tailbud. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/541363v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@abb6fborg.highwire.dtl.DTLVardef@17a297eorg.highwire.dtl.DTLVardef@13a454borg.highwire.dtl.DTLVardef@9b699d_HPS_FORMAT_FIGEXP M_FIG C_FIG Summary statementThis study employs a mathematical model to investigate the interplay between morphogen gradients and tissue mechanics in regulating the collective cell movements that drive hindgut morphogenesis in the chick embryo.