Abstract
A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis.
Highlights
The cellular processes by which a field of cells develops into a spatially-organized tissue have traditionally been split into two distinct questions: pattern formation and morphogenesis
Growth and patterning occur along three major axes: the proximal-distal axis (PD) that goes from the body to the finger tip; the anterior-posterior axis (AP) going from the thumb to the little finger and the dorsal-ventral axis (DV), going from the palm to the dorsal part of the limb
We present here a new computational method that estimates the velocity vector field of limb tissue movement by using 2 experimental constraints: a sequence of experimental limb morphologies, and long-term clonal data
Summary
The cellular processes by which a field of cells develops into a spatially-organized tissue have traditionally been split into two distinct questions: pattern formation and morphogenesis. The second focuses on the cellular behaviors that physically drive growth and shaping of multicellular structures While these two processes can be considered to be conceptually separated, in practice they usually occur simultaneously and are believed to be tightly coordinated. Limb development starts around 9 days post fertilization with the protrusion of a mass of undifferentiated mesenchymal cells from the lateral plate mesoderm of the embryo. This structure, known as the limb bud, is able to grow and organize itself in less than 3 days to determine most of the structures found in the adult limb (tendons, skeleton, dermis etc.). A crucial step to better understand both limb morphogenesis and patterning is to accurately map tissue movements over space and time
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