Learning a conserved mechanism for early neuroectoderm morphogenesis

TL;DR

This study uncovers a conserved BMP-driven signaling cascade that orchestrates early neuroectoderm morphogenesis by regulating cytoskeletal dynamics, with implications across species from flies to humans.

Contribution

It introduces a novel mechanochemical model linking BMP signaling to cytoskeletal dynamics during neuroectoderm formation, validated through machine learning and mutant analysis.

Findings

BMP sets initial conditions for morphogenetic dynamics

A signaling cascade from BMP to E-cadherin to myosin was identified

Conserved mechanisms are observed from Drosophila to human neural tissues

Abstract

Morphogenesis is the process whereby the body of an organism develops its target shape. The morphogen BMP is known to play a conserved role across bilaterian organisms in determining the dorsoventral (DV) axis. Yet, how BMP governs the spatio-temporal dynamics of cytoskeletal proteins driving morphogenetic flow remains an open question. Here, we use machine learning to mine a morphodynamic atlas of Drosophila development, and construct a mathematical model capable of predicting the coupled dynamics of myosin, E-cadherin, and morphogenetic flow. Mutant analysis shows that BMP sets the initial condition of this dynamical system according to the following signaling cascade: BMP establishes DV pair-rule-gene patterns that set-up an E-cadherin gradient which in turn creates a myosin gradient in the opposite direction through mechanochemical feedbacks. Using neural tube organoids, we argue that BMP, and the signaling cascade it triggers, prime the conserved dynamics of neuroectoderm morphogenesis from fly to humans.