Insights into digit evolution from a fate map study of the forearm using Chameleon, a new transgenic chicken line.

The cellular and genetic networks that contribute to the development of the zeugopod (radius and ulna of the forearm, tibia and fibula of the leg) are not well understood, although these bones are susceptible to loss in congenital human syndromes and to the action of teratogens such as thalidomide. Using a new fate-mapping approach with the Chameleon transgenic chicken line, we show that there is a small contribution of SHH-expressing cells to the posterior ulna, posterior carpals and digit 3. We establish that although the majority of the ulna develops in response to paracrine SHH signalling in both the chicken and mouse, there are differences in the contribution of SHH-expressing cells between mouse and chicken as well as between the chicken ulna and fibula. This is evidence that, although zeugopod bones are clearly homologous according to the fossil record, the gene regulatory networks that contribute to their development and evolution are not fixed.

Zebrafish neuromesodermal progenitors undergo a critical state transition in vivo.

The transition state model of cell differentiation proposes that a transient window of gene expression stochasticity precedes entry into a differentiated state. Here, we assess this theoretical model in zebrafish neuromesodermal progenitors (NMps) in vivo during late somitogenesis stages. We observed an increase in gene expression variability at the 24 somite stage (24ss) before their differentiation into spinal cord and paraxial mesoderm. Analysis of a published 18ss scRNA-seq dataset showed that the NMp population is noisier than its derivatives. By building in silico composite gene expression maps from image data, we assigned an 'NM index' to in silico NMps based on the expression of neural and mesodermal markers and demonstrated that cell population heterogeneity peaked at 24ss. Further examination revealed cells with gene expression profiles incongruent with their prospective fate. Taken together, our work supports the transition state model within an endogenous cell fate decision making event.

Quantitative Experimental Embryology: A Modern Classical Approach.

Experimental Embryology is often referred to as a classical approach of developmental biology that has been to some extent replaced by the introduction of molecular biology and genetic techniques to the field. Inspired by the combination of this approach with advanced techniques to uncover core principles of neural crest development by the laboratory of Roberto Mayor, we review key quantitative examples of experimental embryology from recent work in a broad range of developmental biology questions. We propose that quantitative experimental embryology offers essential ways to explore the reaction of cells and tissues to targeted cell addition, removal, and confinement. In doing so, it is an essential methodology to uncover principles of development that remain elusive such as pattern regulation, scaling, and self-organisation.

Building consensus in neuromesodermal research: Current advances and future biomedical perspectives.

The development of the vertebrate body axis relies on the activity of different populations of axial progenitors, including neuromesodermal progenitors. Currently, the term 'Neuromesodermal progenitors' is associated with various definitions. Here, we use distinct terminologies to highlight advances in our understanding of this cell type at both the single-cell and population levels. We discuss how these recent insights prompt new opportunities to address a range of biomedical questions spanning cancer metastasis, congenital disorders, cellular metabolism, regenerative medicine, and evolution. Finally, we outline some of the major unanswered questions and propose future directions at the forefront of neuromesodermal research.