Developmental Patterning Research Articles

Towards a physical understanding of developmental patterning.

The temporal coordination of events at cellular and tissue scales is essential for the proper development of organisms, and involves cell-intrinsic processes that can be coupled by local cellular signalling and instructed by global signalling, thereby creating spatial patterns of cellular states that change over time. The timing and structure of these patterns determine how an organism develops. Traditional developmental genetic methods have revealed the complex molecular circuits regulating these processes but are limited in their ability to predict and understand the emergent spatio-temporal dynamics. Increasingly, approaches from physics are now being used to help capture the dynamics of the system by providing simplified, generic descriptions. Combined with advances in imaging and computational power, such approaches aim to provide insight into timing and patterning in developing systems.

A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

Developmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. We focus here on a population of epidermal cells, the seam cells, which show stem cell-like behaviour and divide symmetrically and asymmetrically over post-embryonic development to generate epidermal and neuronal tissues. We have conducted a mutagenesis screen to identify mutants that introduce phenotypic variability in the normally invariant seam cell population. We report here that a null mutation in the fusogen eff-1 increases seam cell number variability. Using time-lapse microscopy and single molecule fluorescence hybridisation, we find that seam cell division and differentiation patterns are mostly unperturbed in eff-1 mutants, indicating that cell fusion is uncoupled from the cell differentiation programme. Nevertheless, seam cell losses due to the inappropriate differentiation of both daughter cells following division, as well as seam cell gains through symmetric divisions towards the seam cell fate were observed at low frequency. We show that these stochastic errors likely arise through accumulation of defects interrupting the continuity of the seam and changing seam cell shape, highlighting the role of tissue homeostasis in suppressing phenotypic variability during development.

A signalling cascade for Ral

ABSTRACT Ras is the most mutated oncoprotein in cancer. Among the three oncogenic effectors of Ras – Raf, PI3 Kinase and RalGEF>Ral – signalling through RalGEF>Ral (Ras-like) is by far the least well understood. A variety of signals and binding partners have been defined for Ral, yet we know little of how Ral functions in vivo. This review focuses on previous research in Drosophila that defined a function for Ral in apoptosis and established indirect relationships among Ral, the CNH-domain MAP4 Kinase misshapen, and the JNK MAP kinase basket. Most of the described signalling components are not essential in C. elegans, facilitating subsequent analysis using developmental patterning of the C. elegans vulval precursor cells (VPCs). The functions of two paralogous CNH-domain MAP4 Kinases were defined relative to Ras>Raf, Notch and Ras>RalGEF>Ral signalling in VPCs. MIG-15, the nematode ortholog of misshapen, antagonizes both the Ral-dependent and Ras>Raf-dependent developmental outcomes. In contrast, paralogous GCK-2, the C. elegans ortholog of Drosophila happyhour, propagates the 2°-promoting signal of Ral. Manipulations via CRISPR of Ral signalling through GCK-2 coupled with genetic epistasis delineated a Ras>RalGEF>Ral>Exo84>GCK-2>MAP3KMLK−1> p38PMK−1 cascade. Thus, genetic analysis using invertebrate experimental organisms defined a cascade from Ras to p38 MAP kinase.

Influence of Hoxa11 and Hoxd11 on Calcaneus Growth and Ossification

Hox genes are key developmental patterning genes that impact segmental identity and skeletal patterning. While Hox11 genes are known to be expressed around the developing calcaneus bone of the ankle, previous studies on mice with Hox11 mutations have indicated that calcaneus morphology is not affected until both Hoxa11 and Hoxd11are knocked out, at which point the calcaneus and talus fail to form.The pisiform bone, a wrist bone that is paralogous to the calcaneus, exhibits substantial morphological and growth plate alterations with Hox11 mutations. We have previously shown that some length differences are present in the adult calcanei of mice with Hoxa11 and Hoxd11 loss-of-function mutations. The present study investigates whether or not the calcaneus growth plate is altered by Hoxa11 and Hoxd11 loss-of-function mutation. We conducted histological analysis of the calcaneus growth plate in juvenile mice with Hoxa11 and Hoxd11 loss-of-function mutations and compared them to ossification patterns observed in whole-mount specimens that were cleared and stained with alizarin red and alcian blue to visualize bone and cartilage, respectively. Histological analysis reveals that early calcaneus growth plates preserve the hypertrophic and proliferative growth plate zones. This is in contrast to the pisiform and likely a result of Hoxc gene expression in the hind limb but not the forelimb. The shape of the epiphyseal cartilage, however, differs greatly in mice with a combined three loss-of-function alleles between Hoxa11 and Hoxd11. In these mice, the calcaneus epiphyseal cartilage is conical shaped with an elongated region of reserve zone chondrocytes. The ossification front and calcaneal tendon insertion are also altered compared to wild type specimens. The first evidence of calcaneal epiphysis ossification appears at P9 in some Hox11 mutant mice, while it typically appears at P11 in wild type specimens. By P17, the epiphysis appears to be larger in specimens with both Hoxa11 and Hoxd11 mutations compared to wild type. These results indicate that the calcaneus growth plate is more resilient to Hox11 mutations than the pisiform, but that the calcaneus exhibits morphological changes and evidence of altered ossification timing with fewer loss-of-function alleles than identified by previous studies.

Epigenetic Toxicity: Preconception Paternal Alcohol Exposure and the Programming of Offspring Birth Defects

Paternally inherited alterations in epigenetic programming are emerging as a relevant factor in numerous developmental disorders. Despite the exclusive association of fetal alcohol spectrum disorders (FASDs) with maternal drinking, research from our lab indicates that paternal alcohol use is a relevant factor in this debilitating condition. Using an established mouse model, our group has linked preconception paternal alcohol use to sex-specific patterns of both fetal and postnatal growth restriction, as well as long-term metabolic defects in the next generation. These phenotypic changes associate with altered placentation and programmed changes in gene expression that arise during fetal gestation and persist into adulthood. In addition to growth restriction, FASD patients exhibit distinctive craniofacial malformations and central nervous system defects. Although primarily examined in the context of early-life exposures, research now suggests that altered epigenetic programming may drive the emergence of several FASD phenotypes. Accordingly, we hypothesized that within the offspring of ethanol-exposed males, inherited epigenetic changes may negatively influence the transcriptional programs regulating the structural organization and developmental patterning of the face. Using a C57BL/6J mouse model of chronic paternal alcohol exposure, we find that preconception paternal ethanol exposure is associated with reductions in ocular diameter and abnormalities in the patterning of the eye. These defects associate with differential expression of crucial homeobox genes driving craniofacial development, including Msh Homeobox 1 and Msh Homeobox 2 (Msx1 and Msx2) as well as the transcriptional regulators Bone Morphogenic Protein 4 (BMP4) and Twist Family BHLH Transcription Factor 1 (Twist1). Preliminary data indicate that alterations in craniofacial patterning correlate with long-term suppression of the genetic pathways controlling oxidative phosphorylation and the oxidative stress response. These persistent epigenetic changes transmit to the offspring via paternally-inherited changes in histone post-translational modifications and the non-coding RNA profile of sperm. In this talk, I will describe our ongoing efforts to identify the epigenetic mechanisms by which paternally-inherited phenotypes transmit to the offspring and how these alterations in paternal programming influence fetal development. Our observations challenge the prevailing paradigm that alcohol-related congenital disabilities are exclusively attributable to maternal alcohol consumption and reveal paternal life history is relevant to FASD developmental defects.

MLL1-COMPASS establishes developmental patterning of the memory CD8 T cell compartment and ensures regenerative immunity.

Abstract CD8+ T cells with stem cell-like qualities (TSTEM) provide central memory following resolved intracellular infections, and serve as progenitor cells that sustain effector-like cell development during chronic infections and tumors, both naturally and in response to immunotherapeutic PD-1 blockade. However, the chromatin regulatory factors (CRFs) and transcriptional programs that establish TSTEM cell differentiation are unclear. Using an RNA interference screen of all CRFs we discovered that Mixed Lineage Leukemia 1 (MLL1) was required in activated CD8 T cells to promote Id3-GFP reporter expression and to coordinately restrain PD-1, LAG3 and TIM3 expression. Single cell RNA-seq analysis demonstrated Kmt2a (MLL1) was preferentially expressed in P14 CD8 T cells enriched with TSTEM gene expression during lymphocytic choriomeningitis virus (LCMV) infection. P14 CD8 T cells depleted of MLL1 failed to establish TSTEM-like cells, terminally differentiated prematurely, failed to sustain responses to chronic LCMV infection and tumors, and failed to develop central memory subsets during acute LCMV infection. MLL1 preferentially bound transcriptional start sites (TSSs) in CD8 T cells, and was essential for global accumulation of H3K4me3, H4K16ac, and RNA Polymerase II CTD-phosphorylation during TCR stimulation. These results suggest that MLL1-COMPASS organizes TSS activity to establish transcriptional programs that delineate TSTEM and terminal differentiation.

Differential Impact of Hoxa11 and Hoxd11 on Pisiform Ossification and Epiphysis Formation

Hox genes are key developmental patterning genes that impact segmental identity and skeletal patterning. Hox11 genes are known to impact wrist and ankle development and are expressed around the developing pisiform and calcaneus. These paralogous bones in the wrist and ankle are the only carpal and tarsal to form a growth plate in mammals, although humans have lost this growth plate and the associated primary ossification center in the pisiform. Loss-of-function mutations to Hoxa11 and Hoxd11 result in pisiform truncation and appear to also cause at least some disorganization of the growth plate cartilage; however, little is known about the nature of this disorganization or if ossification timing is impacted by Hox11 genes. The present study investigates the role of Hoxa11 and Hoxd11 in pisiform growth plate organization and ossification timing. We conducted histological analysis of the pisiform growth plate in juvenile mice with Hoxa11 and Hoxd11 loss-of-function mutations and compared them to ossification patterns observed in age- and genotype-matched whole-mount specimens that were cleared and stained with Alizarin red and Alcian blue to visualize bone and cartilage, respectively. Histological analysis reveals a dosage-dependent impact of Hox11 mutations on pisiform ossification to both the primary and secondary ossification center. As the number of Hox11 mutation alleles increase, less bone is present in the early primary ossification center compared to age-matched specimens. In specimens with three loss-of-function alleles, no trabeculae or growth plate organization are visible at P9, when both are well established in wild type specimens. Cleared and stained specimens indicate a possible pseudo epiphysis forming with Hoxd11 mutation, while Hoxa11 knockout specimens have not formed any visible epiphysis or calcification by P9. These results indicate that ossification timing and patterns, along with growth plate organization, are affected by Hox11 mutations during early pisiform ossification. Furthermore, Hoxa11 and Hoxd11 alter the pisiform epiphysis differently, suggesting that each plays a specific role in formation of the ossification front and epiphysis ossification either by influencing timing, ossification progression, or both. Further work is needed to understand the mechanisms by which Hox genes impact ossification patterns and timing, as well as the differential roles of Hoxa11 and Hoxd11 in growth plate organization and epiphysis formation.

Conserved and unique transcriptional features of pharyngeal arches in the skate (Leucoraja erinacea) and evolution of the jaw.

The origin of the jaw is a long-standing problem in vertebrate evolutionary biology. Classical hypotheses of serial homology propose that the upper and lower jaw evolved through modifications of dorsal and ventral gill arch skeletal elements, respectively. If the jaw and gill arches are derived members of a primitive branchial series, we predict that they would share common developmental patterning mechanisms. Using candidate and RNAseq/differential gene expression analyses, we find broad conservation of dorsoventral (DV) patterning mechanisms within the developing mandibular, hyoid, and gill arches of a cartilaginous fish, the skate (Leucoraja erinacea). Shared features include expression of genes encoding members of the ventralizing BMP and endothelin signaling pathways and their effectors, the joint markers nkx3.2 and gdf5 and prochondrogenic transcription factor barx1, and the dorsal territory marker pou3f3. Additionally, we find that mesenchymal expression of eya1/six1 is an ancestral feature of the mandibular arch of jawed vertebrates, whereas differences in notch signaling distinguish the mandibular and gill arches in skate. Comparative transcriptomic analyses of mandibular and gill arch tissues reveal additional genes differentially expressed along the DV axis of the pharyngeal arches, including scamp5 as a novel marker of the dorsal mandibular arch, as well as distinct transcriptional features of mandibular and gill arch muscle progenitors and developing gill buds. Taken together, our findings reveal conserved patterning mechanisms in the pharyngeal arches of jawed vertebrates, consistent with serial homology of their skeletal derivatives, as well as unique transcriptional features that may underpin distinct jaw and gill arch morphologies.

A new miniature Pristella (Actinopterygii: Characiformes: Characidae) with reversed sexual dimorphism from the rio Tocantins and rio São Francisco basins, Brazil

A new species of the genus Pristella Eigenmann, 1908 (Pristella crinogi sp. nov.) is described from the middle rio Tocantins and middle rio São Francisco basins, Brazil. The new species can be diagnosed from its two congeners, Pristella ariporo Conde-Saldaña, Albornoz-Garzón, García-Melo, Villa-Navarro, Mirande, and Lima, 2019 and Pristella maxillaris (Ulrey, 1894), by a combination of color pattern and teeth morphology characters. A phylogenetic analysis of the genus recovered P. crinogi as the sister taxa of P. ariporo. Pristella crinogi, along with P. ariporo, are the first characiform fishes, and one of the first bony fishes, to be reported as presenting a reversed sexual dimorphism, with females presenting a more developed color pattern than males. Comments on the miniaturization of the species, as well as remarks on the biogeography of the genus Pristella, are presented.

Transcription factor encoding of neuron subtype: Strategies that specify arbor pattern

Dendrite and axon arbors form scaffolds that connect a neuron to its partners; they are patterned to support the specific connectivity and computational requirements of each neuron subtype. Transcription factor networks control the specification of neuron subtypes, and the consequent diversification of their stereotyped arbor patterns during differentiation. We outline how the differentiation trajectories of stereotyped arbors are shaped by hierarchical deployment of precursor cell and postmitotic transcription factors. These transcription factors exert modular control over the dendrite and axon features of a single neuron, create spatial and functional compartmentalization of an arbor, instruct implementation of developmental patterning rules, and exert operational control over the cell biological processes that construct an arbor.

Time and space in segmentation.

Arthropod segmentation and vertebrate somitogenesis are leading fields in the experimental and theoretical interrogation of developmental patterning. However, despite the sophistication of current research, basic conceptual issues remain unresolved. These include: (i) the mechanistic origins of spatial organization within the segment addition zone (SAZ); (ii) the mechanistic origins of segment polarization; (iii) the mechanistic origins of axial variation; and (iv) the evolutionary origins of simultaneous patterning. Here, I explore these problems using coarse-grained models of cross-regulating dynamical processes. In the morphogenetic framework of a row of cells undergoing axial elongation, I simulate interactions between an ‘oscillator’, a ‘switch’ and up to three ‘timers’, successfully reproducing essential patterning behaviours of segmenting systems. By comparing the output of these largely cell-autonomous models to variants that incorporate positional information, I find that scaling relationships, wave patterns and patterning dynamics all depend on whether the SAZ is regulated by temporal or spatial information. I also identify three mechanisms for polarizing oscillator output, all of which functionally implicate the oscillator frequency profile. Finally, I demonstrate significant dynamical and regulatory continuity between sequential and simultaneous modes of segmentation. I discuss these results in the context of the experimental literature.

Dynamics of hunchback translation in real-time and at single-mRNA resolution in the Drosophila embryo.

ABSTRACTThe Hunchback (Hb) transcription factor is crucial for anterior-posterior patterning of the Drosophila embryo. The maternal hb mRNA acts as a paradigm for translational regulation due to its repression in the posterior of the embryo. However, little is known about the translatability of zygotically transcribed hb mRNAs. Here, we adapt the SunTag system, developed for imaging translation at single-mRNA resolution in tissue culture cells, to the Drosophila embryo to study the translation dynamics of zygotic hb mRNAs. Using single-molecule imaging in fixed and live embryos, we provide evidence for translational repression of zygotic SunTag-hb mRNAs. Whereas the proportion of SunTag-hb mRNAs translated is initially uniform, translation declines from the anterior over time until it becomes restricted to a posterior band in the expression domain. We discuss how regulated hb mRNA translation may help establish the sharp Hb expression boundary, which is a model for precision and noise during developmental patterning. Overall, our data show how use of the SunTag method on fixed and live embryos is a powerful combination for elucidating spatiotemporal regulation of mRNA translation in Drosophila.

Thermal and boundary layer flow analysis for MWCNT-SiO2 hybrid nanoparticles: An experimental thermal model

The nanomaterials, due to improved thermal consequences, intended the researcher’s attention in recent decade due to several engineering applications. The concept of boundary layer is quite necessitated in era of engineering like furnishing of different objects designs to control the drag force in case of flow of various working fluids. This theoretical nanofluid continuation aims to access the thermal aspects of hybrid nanomaterials in flow of non-Newtonian fluids confined by a moving belt. The hybrid characteristics of hybrid nanofluid are examined with multiple suspension of Silicon dioxide (SiO2) and multi-walled carbon nanotubes (MWCNTs) with base material ethylene glycol (EG) and water. The conservation laws and thermal features are incorporated to model the governing equations of hybrid nanofluid problem. The mathematical relations for model’s parameters are developed with applications of experimental modeling and justifications. The results in the form of velocity and temperature profiles for boundary layer regions are calculated with influence of different nanoparticles volume fractions and displaced by graphically. The altered developed pattern of momentum as well as thermal boundary layer thickness is accessed with associated boundary growth.

Possible favorable lifestyle changes owing to the coronavirus disease 2019 (COVID-19) pandemic among middle-aged Japanese women: An ancillary survey of the TRF-Japan study using the original "Taberhythm" smartphone app.

Coronavirus disease 2019 (COVID-19) has had a global effect on people's lifestyles. Many people have become physically inactive and developed irregular eating patterns, which leads to unhealthier lifestyles and aggravation of lifestyle-related diseases; these in turn increase the severity of COVID-19. Prior to the COVID-19 pandemic, we developed a smartphone application called "Taberhythm" to investigate eating patterns, physical activity, and subjective feelings of happiness. We aimed to compare lifestyle data before and during the first phase of the COVID-19 pandemic to objectively assess lifestyle changes during quarantine. A total of 464 smartphone users (346 women, 35 ± 12 years old, body mass index [BMI] 23.4 ± 4.5) participated in Period A (January 7 to April 28, 2019) and 622 smartphone users (533 women, 32 ± 11 years old, BMI 23.3 ± 4.0) participated in Period B (January 6 to April 26, 2020). Compared with Period A, there was a sharp decline in physical activity during Period B (4642 ± 3513 vs. 3814 ± 3529 steps/day, p<0.001), especially during the final 9 weeks in both periods (4907 ± 3908 vs. 3528 ± 3397 steps/day, p<0.001); however, there were large variations in physical activity among participants. We found a surprising trend during Period B toward increased happiness among women aged 30-50 years, the group most affected by stay-at-home policies that led to working from home and school closure. Moreover, daily eating duration declined in this population. Additionally, there was a positive association of happiness with steps per day in Period B (ρ = 0.38, p = 0.02). Despite the many negative effects of the COVID-19 pandemic, subjective feelings of happiness among middle-aged Japanese women tended to increase, which indicates that some favorable lifestyle changes that could be adopted during quarantine in the ongoing COVID-19 pandemic.

From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell-based Embryo Models along the Embryonic Timeline.

In recent years, stem cell‐based models that reconstruct mouse and human embryogenesis have gained significant traction due to their near‐physiological similarity to natural embryos. Embryo models can be generated in large numbers, provide accessibility to a variety of experimental tools such as genetic and chemical manipulation, and confer compatibility with automated readouts, which permits exciting experimental avenues for exploring the genetic and molecular principles of self‐organization, development, and disease. However, the current embryo models recapitulate only snapshots within the continuum of embryonic development, allowing the progression of the embryonic tissues along a specific direction. Hence, to fully exploit the potential of stem cell‐based embryo models, multiple important gaps in the developmental landscape need to be covered. These include recapitulating the lesser‐explored interactions between embryonic and extraembryonic tissues such as the yolk sac, placenta, and the umbilical cord; spatial and temporal organization of tissues; and the anterior patterning of embryonic development. Here, it is detailed how combinations of stem cells and versatile bioengineering technologies can help in addressing these gaps and thereby extend the implications of embryo models in the fields of cell biology, development, and regenerative medicine.

Drosophila Homeodomain-Interacting Protein Kinase (Hipk) Phosphorylates the Hippo/Warts Signalling Effector Yorkie.

Developmental growth and patterning are regulated by an interconnected signalling network of several pathways. In Drosophila, the Warts (Wts) kinase, a component of the Hippo signalling pathway, plays an essential role in regulating transcription and growth by phosphorylating its substrate Yorkie (Yki). The phosphorylation of Yki critically influences its localisation and activity as a transcriptional coactivator. In this study, we identified the homeodomain-interacting protein kinase (Hipk) as another kinase that phosphorylates Yki and mapped several sites of Yki phosphorylated by Hipk, using in vitro analysis: Ser168, Ser169/Ser172 and Ser255. These sites might provide auxiliary input for Yki regulation in vivo, as transgenic flies with mutations in these show prominent phenotypes; Hipk, therefore, represents an additional upstream regulator of Yki that works in concert with Wts.

Modification of cereal plant architecture by genome editing to improve yields.

We summarize recent genome editing studies that have focused on the examination (or reexamination) of plant architectural phenotypes in cereals and the modification of these traits for crop improvement. Plant architecture is defined as the three-dimensional organization of the entire plant. Shoot architecture refers to the structure and organization of the aboveground components of a plant, reflecting the developmental patterning of stems, branches, leaves and inflorescences/flowers. Root system architecture is essentially determined by four major shape parameters-growth, branching, surface area and angle. Interest in plant architecture has arisen from the profound impact of many architectural traits on agronomic performance, and the genetic and hormonal regulation of these traits which makes them sensitive to both selective breeding and agronomic practices. This is particularly important in staple crops, and a large body of literature has, therefore, accumulated on the control of architectural phenotypes in cereals, particularly rice due to its twin role as one of the world's most important food crops as well as a model organism in plant biology and biotechnology. These studies have revealed many of the molecular mechanisms involved in the regulation of tiller/axillary branching, stem height, leaf and flower development, root architecture and the grain characteristics that ultimately help to determine yield. The advent of genome editing has made it possible, for the first time, to introduce precise mutations into cereal crops to optimize their architecture and close in on the concept of the ideotype. In this review, we consider recent genome editing studies that have focused on the examination (or reexamination) of plant architectural phenotypes in cereals and the modification of these traits for crop improvement.

Arp2/3-dependent mechanical control of morphogenetic robustness in an inherently challenging environment.

SummaryEpithelial sheets undergo highly reproducible remodeling to shape organs. This stereotyped morphogenesis depends on a well-defined sequence of events leading to the regionalized expression of developmental patterning genes that finally triggers downstream mechanical forces to drive tissue remodeling at a pre-defined position. However, how tissue mechanics controls morphogenetic robustness when challenged by intrinsic perturbations in close proximity has never been addressed.Using Drosophila developing leg, we show that a bias in force propagation ensures stereotyped morphogenesis despite the presence of mechanical noise in the environment. We found that knockdown of the Arp2/3 complex member Arpc5 specifically affects fold directionality while altering neither the developmental nor the force generation patterns. By combining in silico modeling, biophysical tools, and ad hoc genetic tools, our data reveal that junctional myosin II planar polarity favors long-range force channeling and ensures folding robustness, avoiding force scattering and thus isolating the fold domain from surrounding mechanical perturbations.

Coordination of local and long range signaling modulates developmental patterning

The development of multicellular organisms relies on correct patterns of cell fates to produce functional tissues in the mature organism. A commonly observed developmental pattern consists of alternating cell fates, where neighboring cells take on distinct cell fates characterized by contrasting gene and protein expression levels, and this cell fate pattern repeats over two or more cells. The patterns produced by these fate decisions are regulated by a small number of highly conserved signaling networks, some of which are mediated by long range diffusible signals and others mediated by local contact-dependent signals. However, it is not completely understood how local and long range signals associated with these networks interact to produce fate patterns that are both robust and flexible. Here we analyze mathematical models to investigate the patterning of cell fates in an array of cells, focusing on a two cell repeating pattern. Bifurcation analysis of a multicellular ODE model, where we consider the cells as discrete compartments, suggests that cells must balance sensitivity to external signals with robustness to perturbations. To focus on the patterning dynamics close to the bifurcation point, we derive a continuum PDE model that integrates local and long range signaling. For those cells with dynamics close to the bifurcation point, sensitivity to long range signals determines how far a pattern extends in space, while the number of local signaling connections determines the type of pattern produced. This investigation provides a general framework for understanding developmental patterning, and how both long range and local signals play a role in generating features observed across biology, such as species differences in nematode vulval development and insect bristle patterning, as well as medically relevant processes such as control of stem cell fate in the intestinal crypt.

Neuromesodermal Progenitors: A Basis for Robust Axial Patterning in Development and Evolution.

During early development the vertebrate embryo elongates through a combination of tissue shape change, growth and progenitor cell expansion across multiple regions of the body axis. How these events are coordinated across the length of the embryo to generate a well-proportioned body axis is unknown. Understanding the multi-tissue interplay of morphogenesis, growth and cell fate specification is essential for us to gain a complete understanding how diverse body plans have evolved in a robust manner. Within the posterior region of the embryo, a population of bipotent neuromesodermal progenitors generate both spinal cord and paraxial mesoderm derivatives during the elongation of the vertebrate body. Here we summarize recent data comparing neuromesodermal lineage and their underlying gene-regulatory networks between species and through development. We find that the common characteristic underlying this population is a competence to generate posterior neural and paraxial mesoderm cells, with a conserved Wnt/FGF and Sox2/T/Tbx6 regulatory network. We propose the hypothesis that by maintaining a population of multi-germ layer competent progenitors at the posterior aspect of the embryo, a flexible pool of progenitors is maintained whose contribution to the elongating body axis varies as a consequence of the relative growth rates occurring within anterior and posterior regions of the body axis. We discuss how this capacity for variation in the proportions and rates of NM specification might have been important allowing for alterations in the timing of embryo growth during evolution.