Indirect development, transdifferentiation and the macroregulatory evolution of metazoans

Abstract

It is proposed here that a biphasic life cycle with partial dedifferentiation of intermediate juvenile or larval stages represents the mainstream developmental mode of metazoans. Developmental plasticity of differentiated cells is considered the essential characteristic of indirect development, rather than the exclusive development of the adult from 'set-aside' cells. Many differentiated larval cells of indirect developers resume proliferation, partially dedifferentiate and contribute to adult tissues. Transcriptional pluripotency of differentiated states has premetazoan origins and seems to be facilitated by histone variant H2A.Z. Developmental plasticity of differentiated states also facilitates the evolution of polyphenism. Uncertainty remains about whether the most recent common ancestor of protostomes and deuterostomes was a direct or an indirect developer, and how the feeding larvae of bilaterians are related to non-feeding larvae of sponges and cnidarians. Feeding ciliated larvae of bilaterians form their primary gut opening by invagination, which seems related to invagination in cnidarians. Formation of the secondary gut opening proceeds by protostomy or deuterostomy, and gene usage suggests serial homology of the mouth and anus. Indirect developers do not use the Hox vector to build their ciliated larvae, but the Hox vector is associated with the construction of the reproductive portion of the animal during feeding-dependent posterior growth. It is further proposed that the original function of the Hox cluster was in gonad formation rather than in anteroposterior diversification.

Figure 1.

Indirect development of the annelid Hydroides elegans. Embryogenesis promptly forms a microscopic feeding trochophore larva. Nourishment ensures the growth and transformation of larval tissues. The trochoblasts are the first larval cells that differentiate (green), and will be discarded during metamorphosis. Differentiated endodermal, ectodermal and mesodermal cells of the larva (black) are ‘recycled’ and contribute to adult transformation. Multipotent adult precursors in the posterior growth zone (PGZ), mesodermal 4d (red) and ectodermal 2d22 (blue), form the segmented portion of the worm, which largely corresponds to the reproductive side of the animal. an, anus; at, apical tuft; bp, blastopore; cb, ciliary band; fg, foregut; hg, hindgut; mg, midgut.

Figure 2.

Outline of the different scenarios for the evolution of indirect development in bilaterians. Evolutionary novelties highlighted in grey. (a) The terminal addition model proposes that the first bilaterians were similar to the larval stage of current indirect developers; the macroscopic adult represents a secondary addendum to the final phase of the life cycle sometime before the bilaterian radiation. (b) The intercalation model proposes a relatively complex protostome/deuterostome ancestor and that the larval stages of protostomes and deuterostomes represent convergent adaptations intercalated during early development. (c) The metazoan biphasic development model proposed here suggests that a differentiated stage at the end of embryogenesis represents the basal condition for metazoans. Adult development proceeds by partial dedifferentiation and subsequent proliferation. In direct developers, the intermediate differentiated stage is similar to the adult; the differentiated stage is a juvenile. The evolution of distinct specializations of the intermediate differentiated stage generates a larval stage.

Figure 3.

Similar gastrulation by invagination of indirectly developing bilaterians and cnidarians may proceed by ancestral developmental programmes. If this is the case, then the core GRNs for gastrulation by invagination should be conserved between protostomes, deuterostomes and cnidarians. If, on the contrary, gastrulation by invagination in protostomes and deuterostomes secondarily evolved from gastrulation in acoels, then substantial variation of core GRNs is expected. In acoels, ingression of endoderm precursors proceeds during cleavage, the blastopore does not correspond to the mouth and there is no endodermal epithelium, only a gut syncytium (gs). For comparative purposes, the cnidarian larva settles to a floating substrate. Regulatory gene expression suggests the correspondence of the dorsal side and the blastopore of indirectly developing protostomes and deuterostomes. The protostome blastopore forms the mouth and the deuterostome blastopore forms the anus. Illuminated ovals represent adult precursors that generate the posterior portions of the respective adults, the associated black arrows represent the ‘Hox vectors’ and posterior growth zones (PGZs). Grey arrows represent gastrulation in the different groups. ap, adult precursor; at, apical tuft; bp, blastopore; cb, ciliary band; gs, gut syncytium; m, mouth; mg, midgut.

Figure 4.

General outline of the larva-to-adult transformation in indirect development. The multi-potent zygote generates a differentiated larva during embryogenesis. Larval-specific tissues (green) are discarded during metamorphosis. Some differentiated larval organs resume proliferation and contribute to adult transformation (yellow, blue and red). Yellow and blue tissues partially dedifferentiate and redifferentiate into related fates (light blue and orange). Substantial regions of the adult derive from multipotent precursors that do not contribute to differentiated larval fates (multi-coloured cells). Maintenance and homeostasis of adult organs is accomplished by a combination of stem cells and the same mechanisms of dedifferentiation–proliferation that constructed the adult.

Figure 5.

Evolution of indirect development. (a) Early metazoans with similar juvenile and adult stages. Adult development proceeds by general growth of differentiated juvenile cells and multipotent cells that are precursors of reproduction-related organs. (b) Indirect development evolves by specializing the juvenile stage to the point of being distinct from the adult (larval stage). Adult specializations also evolve during the second developmental phase, further enhancing differences between larva and adult. (c) Evolution of indirect development by increasing the resources of the egg, which allows elimination of early feeding specializations (elimination of the larval stage). (d) ‘Insect variant’ for evolution of indirect development also proceeds by specializing the juvenile stage and the adult stage.

Figure 6.

Hypothesis for the ancestral association of the Hox cluster with the reproductive side of the animal. (a) In early metazoans, Hox gene precursors had multiple developmental roles, which probably included gonad formation, and, in our illustration, sensory epithelium development. (b) Hox gene dosage after duplication would result in developmental changes in the structures formed; in this case, enhanced gonad and sensory organ development. Autoregulatory interactions become intergenic interactions. Temporal colinearity may concomitantly result as a byproduct of distance-dependent chromatin regulatory functions previously in place or after the asymmetric loss of intergenic regulatory interactions. (c) The duplicates undergo subfunctionalization of the original coding and regulatory multi-functionality; that is, the new genes independently adopt specializations within their original functions. (d,e) Additional tandem duplication and subsequent coding and regulatory subfunctionalization. (e,f) Once in place, recruitment of vectorial Hox cluster gene expression to anteroposterior diversification is possible. Legs, wings and sensory bristles can be differentially deployed along the anteroposterior axis. In (c–e), protein evolution is driven by functional specializations outside the colinear domain of expression.