In Development this week (Vol. 144, Issue 3)

Here are the highlights from the current issue of Development:

Evolving an atypical developmental programme with IMM

The brown alga Ectocarpus has alternating haploid (gametophyte) and diploid (sporophyte) generations. Morphologically, these are distinguished by a more complex system of basal filaments in the sporophyte, initiated via symmetric divisions before the apical-basal axis is defined and the upright filaments form. This mode of development is unusual – in most brown algae, and in the Ectocarpus gametophyte generation, the first division is asymmetric to establish the apical-basal axis. The immediate upright (imm) mutation of Ectocarpus displays an asymmetric first division, and was initially thought to represent a partial switch from the sporophyte to the gametophyte developmental programme. Here (p. 409), Mark Cock and colleagues identify the gene responsible for this phenotype and provide a detailed analysis of its evolutionary history. The IMM gene is a member of the large, rapidly evolving, EsV-1-7 domain family, which exhibits an unusual distribution across eukaryotic lineages – potentially as a result of horizontal gene transfer. Transcriptional profiling suggests that, rather than imm causing a switch from the sporophyte to the gametophyte programme, the mutation blocks the extensive development of the basal filament system, such that the mutant displays a more canonical mode of sporophyte development. While the molecular and cellular function of IMM has yet to be determined, this gene appears to represent an evolutionary innovation in the Ectocarpus lineage that altered early sporophyte development.

Defining the right MOMent for cell fate decisions

The invariant lineage of C. elegans led to an early assumption that cell fate decisions are largely made cell-autonomously. However, it has subsequently become clear that inductive interactions between cells are essential for fate determination in this system. Moreover, these inductive interactions can be highly complex. The 8-cell stage blastomere, MS, gives rise to a number of body wall muscles. Their appropriate differentiation relies first upon an inhibitory signal from the ABp lineage at early stages, and subsequently upon an activating interaction from the ABa lineage a couple of cell cycles later. It has long been known that the activating interaction depends on Notch activity, but the nature of the signals, and the reason for this complex mechanism of cell fate determination, have remained unclear. Rueyling Lin and colleagues now identify zygotic MOM-2 (a Wnt ligand) as the Notch-dependent signal responsible for both the inhibitory and activating interaction (p. 419). Moreover, they provide evidence that this two-step mechanism is important because early inhibition is required to prevent precocious lineage restriction during this rapid phase of development. These data highlight the complex intercellular interactions, and the robust mechanisms, underlying cell fate determination in even a seemingly simple embryo like that of the worm.

Nan: neomorphic effects in neonatal anaemia

The KLF1 transcriptional regulator is essential for normal red blood cell differentiation, and a particular mutation in this factor is associated with congenital dyserythropoietic anaemia. The Nan mutant mouse, in which the same amino acid is mutated and which displays a semi-dominant phenotype, serves as a valuable model for this disorder. It is known that the mutant protein, Nan-KLF1, can only bind a subset of target sites as compared with the wild type, and this leads to changes in downstream gene expression in heterozygous animals – due at least partly to effects of Nan-KLF1 on the target genes whose sites it can no longer bind. James Bieker and colleagues have recently discovered that the Nan-KLF1 variant can also bind a target sequence not recognised by wild-type KLF1. Now (p. 430), they investigate the phenotypic consequences of this. Importantly, they observe neomorphic expression of a number of genes in Nan/+ heterozygotes, which appears to be due to ectopic binding of Nan-KLF1 to these new target sequences. The downstream genes affected include a number of secreted factors, such as hepcidin – a regulator of cellular iron use – and interferon regulatory factor 7 (IRF7). Thus, Nan heterozygosity in the erythropoietic lineage can confer systemic effects via the inappropriate expression of secreted factors.

PLUS:

Trends in tissue repair and regeneration

The 6th EMBO conference on the Molecular and Cellular Basis of Regeneration and Tissue Repair took place in Paestum (Italy) in September, 2016. As summarised in the Meeting Review by Galliot, Crescenzi, Jacinto, and Tajbakhsh, the scientists who attended discussed the importance of plasticity, biophysical aspects of regeneration, injury-induced immune responses, strategies to reactivate regeneration, links between regeneration and ageing, and the impact of non-mammalian models on regenerative medicine.

Formative pluripotency: the executive phase in a developmental continuum

The regulative capability of single cells to give rise to all primary embryonic lineages is termed pluripotency.  Two phases of pluripotency, called naïve and primed, have previously been described. In his Hypothesis article, Austin Smith describes a third phase, called formative pluripotency, that is proposed to exist as part of a developmental continuum between the naïve and primed phases.

Cellular and molecular mechanisms of tooth root development

The tooth root is an integral, functionally important part of our dentition, and understanding how roots develop and how they can be bioengineered is of great interest in the field of regenerative medicine. In their Review article, Yang Chai and colleagues discuss recent advances in understanding the cellular and molecular mechanisms underlying tooth root formation.

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