Delayed transition to new cell fates during cellular reprogramming

Abstract

In many embryos specification toward one cell fate can be diverted to a different cell fate through a reprogramming process. Understanding how that process works will reveal insights into the developmental regulatory logic that emerged from evolution. In the sea urchin embryo, cells at gastrulation were found to reprogram and replace missing cell types after surgical dissections of the embryo. Non-skeletogenic mesoderm (NSM) cells reprogrammed to replace missing skeletogenic mesoderm cells and animal caps reprogrammed to replace all endomesoderm. In both cases evidence of reprogramming onset was first observed at the early gastrula stage, even if the cells to be replaced were removed earlier in development. Once started however, the reprogramming occurred with compressed gene expression dynamics. The NSM did not require early contact with the skeletogenic cells to reprogram, but the animal cap cells gained the ability to reprogram early in gastrulation only after extended contact with the vegetal halves prior to that time. If the entire vegetal half was removed at early gastrula, the animal caps reprogrammed and replaced the vegetal half endomesoderm. If the animal caps carried morpholinos to either hox11/13b or foxA (endomesoderm specification genes), the isolated animal caps failed to reprogram. Together these data reveal that the emergence of a reprogramming capability occurs at early gastrulation in the sea urchin embryo and requires activation of early specification components of the target tissues.

Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton

“…In the sea urchin, removal of the PMCs at the mesenchyme blastula stage causes secondary mesenchyme cells (SMCs), which usually give rise to nonskeletal mesodermal cells, to differentiate into skeletogenic cells [ 34 ]. During this process, alx1 is expressed in transfating SMCs originally lacking expression [ 35 , 36 ]. As the starfish also has mesenchyme cells that ingress from the tip of the archenteron (as do sea urchin SMCs), it is possible that the experimental induction of alx1 expression in starfish larvae induces developmental or genetic changes associated with larval skeletogenesis.…”

The evolution of a new cell type was associated with competition for a signaling ligand

“…In PMC(−) embryos, we originally documented high levels of expression of vegfr-10-Ig in transfating BCs at a relatively late stage, 10–11 hours post–PMC depletion, several hours after alx1 activation [19]. Cheng and coworkers [35], however, used quantitative PCR (QPCR) and WMISH to show that in micromere(−) embryos, which resemble PMC(−) embryos in many respects, expression of vegfr-10-Ig and alx1 was up-regulated at almost the same time. We therefore reexamined the timing of vegfr-10-Ig activation in PMC(−) embryos.…”

Evolution of abbreviated development inHeliocidaris erythrogrammadramatically re-wired the highly conserved sea urchin developmental gene regulatory network to decouple signaling center function from ultimate fate

“…We used this to test the hypothesis that changes in the expression pattern between H. erythrogramma and the ancestral GRN arose concurrently with accelerated development rather than as a difference in the Heliocidaris lineage from other planktotrophic sea urchins where the expression of these genes is well characterized. The T-box gene Tbr was restricted to the SM lineage in euechinoid urchins [51,69] rather than its ancestral role in pan-mesodermal and broad endomesoderm specification [38,60,65,70,71] but it remains indispensable to activate the normal endomesoderm GRN [72,73] and the replacement SM-GRN [47,74]. Tbr ’s placement in the GRN immediately downstream of the HesC/Pmar1 logic gate and integration into a circuit with Alx1 has been proposed as the key event in the evolution of the larval SM cell type [38,45,75].…”

“…We initially considered the hypothesis that H. erythrogramma ’s mesoderm specification GRN recapitulates a well-documented phenomenon in other sea urchins where experimental removal of precursor or differentiated SM cells triggers activation of the SM-GRN in another cell population to produce replacement SM cells [47,74]. However, H. erythrogramma ’s GRN does not match this simple model; it is not merely a planktotrophic euechinoid missing SM cells.…”