ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations.

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations; however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESCs), including a knockout and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR) and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-sequencing analyses in Zscan10-/- mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10.

The evolution of palate shape in the Lepilemur-Cheirogaleidae clade (Primates: Strepsirrhini).

OBJECTIVES: Phylogenies consistently group the folivorous Lepilemur species with the small-bodied insectivorous-frugivorous cheirogaleids. Juvenile lepilemurs and adult cheirogaleids share allometries in most aspects of skull morphology, except the palate. We investigated potential influences on palate shape in these taxa and several outgroups using geometric morphometrics. MATERIALS AND METHODS: Our sample included representatives of four extant strepsirrhine families, Cheirogaleidae (including Lepilemurinae), Lemuridae, Indriidae, and Galagidae, and one subfossil Megaladapis. Our dataset comprised 32 landmarks collected from 397 specimens representing 15 genera and 28 species, and was analyzed using generalized procrustes analyses and between group principal component analysis. We explored the influence of size, phylogeny, diet, and the propagation of loud vocalizations on palate shape. RESULTS: While congeneric species clustered within the morphospace, the phylomorphospace did not mirror molecular phylogenetic hypotheses of higher-order relationships. Four palate forms were distinguished within the Cheirogaleidae. Diet, strongly linked to body size, had the single greatest influence on palate shape. The production of long-distance advertisement calls was most often associated with positive scores on the PC1 axis. DISCUSSION: Our results suggest that the extensive variation in palate shape among Cheirogaleidae is related to dietary shifts that accompanied changes in body size during the clade's radiation. Molecular phylogenies indicate that cheirogaleid diversification involved repeated dwarfing events, which in turn drove dietary shifts from ancestral folivory-frugivory to frugivory, gummivory, and faunivory in the descendant species. The elongated Lepilemur palate is probably related to accelerated eruption of the cheek teeth to render juveniles competent to shear leaves upon weaning.

Middle ear pneumatization in nonhuman primates: A comparative analysis.

OBJECTIVES: We test the effects of body mass and phylogeny on middle ear cavity pneumatization, and the role of pneumatization in hearing function, spanning the anatomical, ecological, and behavioral diversity of nonhuman primates. MATERIALS AND METHODS: All cavities were segmented in middle ear scans of 96 specimens, from 12 strepsirrhine and 15 haplorhine extant species. We measured the tympanic cavity (TC) separately, and all other middle ear spaces together (MES), calculating the degree of pneumatization with the surface area-to-volume ratio. We tested body mass effect with linear regression; we evaluated the phylogenetic signal and selection patterns, using a Kappa statistic test, and Ornstein-Uhlenbeck models (OU). We investigated the link between pneumatization and hearing sensitivity using phylogenetic regression. RESULTS: Testing body mass reveals an allometric pattern for both TC and MES dimensions. Degree of pneumatization in MES is dependent on body mass in haplorhines: larger animals have more pneumatized MES. Differences at various taxonomic ranks were observed for MES, while no phylogenetic influence was observed for TC. Infraorder selection patterns are different. Auditory performance is significantly related to degree of pneumatization, indicating that a pneumatized middle ear is associated with better perception of low frequencies. DISCUSSION: Pneumatization in MES is under differential selective pressure, indicating several optima for this trait. Pneumatization in MES probably modifies hearing sensitivity through pressure regulation mechanisms, auditory bulla size reduction, and frequency modulation. This could explain strepsirrhine adaptation to high-frequency perception, while haplorhine auditory perception is adapted to a broader sound range, including high and low frequencies.

A giant among dwarfs: a new species of galago (Primates: Galagidae) from Angola.

OBJECTIVES: Based on vocalization recordings of an unknown galago species, our main objectives were to compare morphology and call structure with known closely-related taxa and describe a new species of galago. MATERIALS AND METHODS: We conducted field surveys in three forest habitats along the escarpment region in western Angola (Kumbira Forest, Bimbe Area, and Northern Scarp Forest), and examined galago specimens from museums worldwide. We digitized and analyzed calls using Avisoft SASLab Pro software. We also compared museum specimens from Angola with other Galago and Galagoides specimens, and conducted comparative analyses (ANOVA and between group principle component analysis) based on a set of twelve linear measurements of skulls and teeth. RESULTS: We describe the new species to which we give the name Angolan dwarf galago, Galagoides kumbirensis sp. nov. The new species has a loud and characteristic crescendo call, used by other Galagoides spp. (sensu stricto) in West Africa to attract companions and repel rivals. However, this call shows species-typical differences from its closest relatives. Galagoides kumbirensis sp. nov. is also distinguished by differences in the skull morphology, pelage color and facial markings, as well as a larger body size, similar to that of Galago moholi, which is not known to be sympatric. CONCLUSION: This discovery points to the importance of Angolan forests as refuges for endemic biodiversity. These forests are under severe threat from overexploitation, and there is an urgent need to establish conservation measures and designate protected areas.

Effect of temperature and social environment on worker size in the ant Temnothorax nylanderi.

Warm temperatures decrease insect developmental time and body size. Social life could buffer external environmental variations, especially in large social groups, either through behavioral regulation and compensation or through specific nest architecture. Mean worker size and distribution of worker sizes within colonies are important parameters affecting colony productivity as worker size is linked to division of labor in insect societies. In this paper, we investigate the effect of stressful warm temperatures and the role of social environment (colony size and size of nestmate workers) on the mean size and size variation of laboratory-born workers in the small European ant Temnothorax nylanderi. To do so, we reared field-collected colonies under medium or warm temperature treatments after having marked the field-born workers and removed the brood except for 30 first instar larvae. Warm temperature resulted in the production of fewer workers and a higher adult mortality, confirming that this regime was stressful for the ants. T. nylanderi ants followed the temperature size rule observed in insects, with a decreased developmental time and mean size under warm condition. Social environment appeared to play an important role as we observed that (i) larger colonies buffered the effect of temperature better than smaller ones (ii) colonies with larger workers produced larger workers whatever the rearing temperature and (iii) the coefficient of variation of worker size was similar in the field and under medium laboratory temperature. This suggests that worker size variation is not primarily due to seasonal environmental fluctuations in the field. Finally, we observed a higher coefficient of variation of worker size under warm temperature. We propose that this results from a disruption of social regulation, i.e. the control of nestmate workers over developing larvae and adult worker size, under stressful conditions.

Characterizing cryptic species: A morphometric analysis of craniodental characters in the dwarf galago genus Galagoides.

OBJECTIVES: The true dwarf galagos of the genus Galagoides, G. demidoff and G. thomasi, are difficult to distinguish morphologically at a specific or subspecific level, and most taxonomic designations are based primarily on geographic localities. We used morphometrics to investigate the morphological diversity of the genus. MATERIALS AND METHODS: We conducted statistical analyses of 12 linear measurements on 290 Galagoides skulls housed in museums worldwide, and assembled body weights for 71 wild caught specimens. We examined sexual dimorphism and specific and subspecific distinctiveness using MANOVA, ANOVA, principle components analysis and canonical variate analysis. RESULTS: We distinguished skulls identified as Galagoides demidoff and G. thomasi with ∼70% reliability, and demonstrated consistently different patterns of static allometry in craniodental variables. Variables supporting specific distinction included M1 width, palate width at P2 , palate (snout) length, length of premaxillary tube, width across mastoids, and total skull length. The type specimens of G. orinus and G. rondoensis were significantly different from G. demidoff and G. thomasi, but grouped with them in a CVA including G. zanzibaricus and G. granti, although molecular studies indicate that their true affiliation is with the latter species. Subspecies within G. demidoff could not be distinguished using craniodental morphometrics. DISCUSSION: Galagoides demidoff and G. thomasi can be distinguished relatively reliably, and are broadly sympatric across western and central Africa. Neither species showed evidence of sexual dimorphism in craniodental size or shape. Size variation has a greater influence on skull morphology in G. demidoff than it has on G. thomasi. Am J Phys Anthropol 158:288-299, 2015. © 2015 Wiley Periodicals, Inc.

Degree of terrestrial activity of the elusive sun-tailed monkey (Cercopithecus solatus) in Gabon: Comparative study of behavior and postcranial morphometric data.

We carried out a multidisciplinary study linking behavioral and morphological data from a little-known guenon species, Cercopithecus solatus, endemic to Gabon. Over a period of 9 months, we documented the pattern of stratum use associated with postural and locomotor behavior by direct observation (650 hrs) of a semi-free-ranging breeding colony. We also conducted a morphometric analysis of the humerus and limb proportions of 90 adult specimens from 16 guenon species, including C. solatus. Field observations indicated that C. solatus monkeys spent a third of their time on the ground, similar to semi-terrestrial guenon species. We detected two patterns of stratum use: at ground level, and in trees, at a height of 3-10 m. The monkeys spent more time on the ground during the dry season than the wet season, feeding mainly at ground level, while resting, and social behaviors occurred more frequently in the tree strata. Our study of humerus size and shape, together with the analysis of limb proportions, indicated morphofunctional adaptation of C. solatus to greater terrestriality than previously thought. We therefore characterize C. solatus as a semi-terrestrial guenon, and propose a new hypothesis for the ancestral condition. By combining behavioral and morphological results, we provide new information about the adaptive strategies of the species, and the evolutionary history of guenons, thus contributing to the conservation of the sun-tailed monkey in the wild.

Deciphering the mandibular shape variation in a group of Malagasy primates using Fourier outline analysis.

OBJECTIVES: Among living Malagasy primates, the family Lemuridae has previously been recognized as presenting a higher mandibular morphological variation than other families. We conducted a quantitative analysis of mandibular size and shape within the five genera (Lemur, Eulemur, Hapalemur, Prolemur, and Varecia) associated with a set of covariables that could explain this variation. MATERIALS AND METHODS: We used Fourier outline analysis on the left hemimandible of 182 specimens covering the Lemuridae family. The influence of the phylogeny but also seven covariables (genus, diet, sex, sexual behavior, mating system, ecoregion, and forest type) on mandibular variation was examined using multivariate statistics and model selection. RESULTS: Our results indicate that the high level of morphological variation within the family, associated with a phylogenetic effect and differences in diet, is due to a strong distinction between the genera Prolemur and Hapalemur and the other genera of the family. A second analysis, correcting this strong effect, indicates that mandibular shape variation is influenced not only by the phylogeny and the diet but by a combination of all the covariables. DISCUSSION: The analysis of morphological variation is a powerful tool with major applications, both for the estimation of biological diversity and for the understanding of the fundamental parameters of species' ecology. Our work indicates that, if mandibular shape variation is mainly driven by dietary adaptation, other variables describing ecology and habitat should be considered and taken into account for an integrative understanding of species resources and the establishment of conservation measures.

A functional multivariate analysis of Mesopithecus (Primates: Colobinae) humeri from the Turolian of Greece.

The genus Mesopithecus is well represented in the late Miocene of Greece by several recognized species. The present paper investigates functional aspects of the humeri of Mesopithecus delsoni/pentelicus, M. pentelicus and M. aff. pentelicus of several Turolian sites from central and northern Greece, using multivariate approaches. For these purposes, we selected significant humeral functional features, which were represented by 23 linear dimensions and three angles on 14 fossil humeri and 104 humeri from 10 genera and 22 species of extant African and Asian Colobines. All size-adjusted measurements were examined through a principal components analysis, followed by a discriminant function analysis, and a canonical variates analysis. All analyses revealed that the selected characters were able to discriminate between extant colobine genera. Functional groups, such as arboreal walking/climbing, arboreal walking/suspensory and semi-terrestrial walking, were set apart from a central cluster formed by the arboreal walking and arboreal walking/terrestrial groups. This cluster also grouped the three studied Mesopithecus species, which were mainly classified as arboreal walkers with significant terrestrial activities. These observations match with paleoenvironmental reconstructions and the suggested opportunistic feeding habits. Moreover, the overall arboreal/terrestrial locomotor tendencies of these fossil forms are discussed in relation to their earlier migration from Africa and later dispersal to eastern and southern Asia.

[Morphologic and genetic differentiation of night monkey (Aotus infulatus, Primates, Platyrrhinians, Cebidae) populations from the right and left banks of Rio Tocantins (Brazil)]. / Différenciation morphologique et génétique des populations de douroucoulis (Aotus infulatus, Primates, Platyrhiniens, Cebidae) provenant des rives droite et gauche du rio Tocantins (Brésil).

The cranial morphology of 28 specimens of night monkeys (genus Aotus) was examined using three-dimensional geometrical morphometrics. New results of the morphological differences between two populations of Aotus infulatus from both banks of the Rio Tocantins are proposed. These morphological results totally agree with the genetic distinction of these populations proposed by Schneider -- and Sampaio --, and probably point out recent rapid evolutive changes for this species. Our morphometric results can be used for taxonomic, but also for medical research, as the susceptibility to malaria of night monkeys is variable between species.

Eocene Paleoecology of Adapis parisiensis (Primate, Adapidae): From Inner Ear to Lifestyle.

European adapids, especially Adapis parisiensis, have been extensively studied over the past two centuries, essentially for taxonomic and phylogenetic purposes. Analyses of dental, cranial, and postcranial morphology have led to various hypotheses about the diet, locomotion, and lifestyle of this fossil primate species. As the morphology of Adapis parisiensis is not directly comparable to any extant species, some interpretations are still debated. The inner ear is crucial to several functional parameters, such as auditory acuity, balance, agility, orientation, and head motion speed during locomotion. We examined the inner ear morphology of Adapis parisiensis in order to make some functional inferences, using µCT techniques to access the internal morphology without damaging the fossil specimens. We analyzed the length and shape of the cochlea, the size of the oval window, and the size and orientation of the semicircular canals of seven Adapis parisiensis crania. Results indicate that the species was more sensitive to high frequencies than low frequencies. Results for locomotion style are different, depending on the method used. Results about the coefficient of agility are in good agreement with previous studies, proposing a slow/medium slow locomotion for the fossil species. In contrast, angular velocity magnitude (AVM) results show a great range of variation in the locomotor repertory for Adapis parisiensis, probably indicating that the model used is not adapted to the study of the fossil record. A comparison to measurements of extant strepsirhines leads us to conclude that Adapis parisiensis was probably monogamous and solitary, with a small home range. Anat Rec, 300:1576-1588, 2017. © 2017 Wiley Periodicals, Inc.