Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal-Glial Synapses and Reduced Expression in Mice.

Mutations in the Neuroligin-3 () gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction, but cellular expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization and immunofluorescence to measure mRNA expression in cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells in both WT and mutant mice. We measured mRNA neuronal and glial expression via quantitative three-dimensional image analysis.

Pluripotent stem cell derived dopaminergic subpopulations model the selective neuron degeneration in Parkinson's disease.

In Parkinson's disease (PD), substantia nigra (SN) dopaminergic (DA) neurons degenerate, while related ventral tegmental area (VTA) DA neurons remain relatively unaffected. Here, we present a methodology that directs the differentiation of mouse and human pluripotent stem cells toward either SN- or VTA-like DA lineage and models their distinct vulnerabilities. We show that the level of WNT activity is critical for the induction of the SN- and VTA-lineage transcription factors Sox6 and Otx2, respectively.

Relationship Between Parent Vowel Hyperarticulation in Infant-Directed Speech and Infant Phonetic Complexity on the Level of Conversational Turns.

When speaking to infants, parents typically use infant-directed speech, a speech register that in several aspects differs from that directed to adults. Vowel hyperarticulation, that is, extreme articulation of vowels, is one characteristic sometimes found in infant-directed speech, and it has been suggested that there exists a relationship between how much vowel hyperarticulation parents use when speaking to their infant and infant language development. In this study, the relationship between parent vowel hyperarticulation and phonetic complexity of infant vocalizations is investigated.

An Association Between Phonetic Complexity of Infant Vocalizations and Parent Vowel Hyperarticulation.

Extreme or exaggerated articulation of vowels, or vowel hyperarticulation, is a characteristic commonly found in infant-directed speech (IDS). High degrees of vowel hyperarticulation in parent IDS has been tied to better speech sound category development and bigger vocabulary size in infants. In the present study, the relationship between vowel hyperarticulation in Swedish IDS to 12-month-old and phonetic complexity of infant vocalizations is investigated.

Expressive vocabulary development in children with moderate hearing loss - the impact of auditory variables and early consonant production.

In this study, the early expressive vocabulary development was investigated in a group of children with moderate hearing loss (HL). Size and development of expressive vocabulary from 18 30 months were analyzed and compared to a group of children with normal hearing (NH). For the children with HL, the impact of auditory variables on number of words were examined.

Dysregulation of the NRG1/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans.

Hirschsprung disease (HSCR) is the most frequent developmental anomaly of the enteric nervous system, with an incidence of 1 in 5000 live births. Chronic intestinal pseudo-obstruction (CIPO) is less frequent and classified as neurogenic or myogenic. Isolated HSCR has an oligogenic inheritance with RET as the major disease-causing gene, while CIPO is genetically heterogeneous, caused by mutations in smooth muscle-specific genes.

Diversification of molecularly defined myenteric neuron classes revealed by single-cell RNA sequencing.

Autonomous regulation of the intestine requires the combined activity of functionally distinct neurons of the enteric nervous system (ENS). However, the variety of enteric neuron types and how they emerge during development remain largely unknown. Here, we define a molecular taxonomy of 12 enteric neuron classes within the myenteric plexus of the mouse small intestine using single-cell RNA sequencing.

Schwann Cell Precursors Generate the Majority of Chromaffin Cells in Zuckerkandl Organ and Some Sympathetic Neurons in Paraganglia.

In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning of midgestation and are the main cellular source of adrenalin and noradrenalin released into the blood stream. In mammals, two different chromaffin organs emerge at a close distance to each other, the adrenal gland and Zuckerkandl organ (ZO).

Molecular Architecture of the Mouse Nervous System.

The mammalian nervous system executes complex behaviors controlled by specialized, precisely positioned, and interacting cell types. Here, we used RNA sequencing of half a million single cells to create a detailed census of cell types in the mouse nervous system. We mapped cell types spatially and derived a hierarchical, data-driven taxonomy.

Introducing WCM-SE: The word complexity measure phonetically justified and adapted to Swedish.

This paper presents the Word Complexity Measure for Swedish (WCM-SE), an adaptation of the original WCM developed for English by Stoel-Gammon. These measures are used to calculate the phonological complexity of words or vocalizations, based on a number of phonological complexity parameters. Each production receives a complexity score based on how many of the parameters are present in the production.

Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage.

Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium.

The development of a vocabulary for PEEPS-SE-profiles of early expressive phonological skills for Swedish.

This paper describes the development of a vocabulary for Profiles of Early Expressive Phonological Skills for Swedish (PEEPS-SE), a tool for assessment of expressive phonology in Swedish-learning children in the age range of 18-36 months. PEEPS-SE is the Swedish version of the original PEEPS, Profiles of Early Expressive Phonological Skills, which uses two age-adequate word lists-a basic word list (BWL) for the assessment of 18-24-month-old children, to which an expanded word list (EWL) is added for assessment of 24-36-month-old children, or children with more than 250 words in their expressive vocabulary. The selection of words in PEEPS-SE is based on two types of criteria: age of acquisition and phonological complexity.

Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System.

Background & Aims: The enteric nervous system (ENS) regulates gastrointestinal function via different subtypes of neurons, organized into fine-tuned neural circuits. It is not clear how cell diversity is created within the embryonic ENS; information required for development of cell-based therapies and models of enteric neuropathies. We aimed to identify proteins that regulate ENS differentiation and network formation.

Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla.

Adrenaline is a fundamental circulating hormone for bodily responses to internal and external stressors. Chromaffin cells of the adrenal medulla (AM) represent the main neuroendocrine adrenergic component and are believed to differentiate from neural crest cells. We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs).

Ascl1 Is Required for the Development of Specific Neuronal Subtypes in the Enteric Nervous System.

Unlabelled: The enteric nervous system (ENS) is organized into neural circuits within the gastrointestinal wall where it controls the peristaltic movements, secretion, and blood flow. Although proper gut function relies on the complex neuronal composition of the ENS, little is known about the transcriptional networks that regulate the diversification into different classes of enteric neurons and glia during development. Here we redefine the role of Ascl1 (Mash1), one of the few regulatory transcription factors described during ENS development.

Pause and utterance duration in child-directed speech in relation to child vocabulary size.

This study compares parental pause and utterance duration in conversations with Swedish speaking children at age 1;6 who have either a large, typical, or small expressive vocabulary, as measured by the Swedish version of the McArthur-Bates CDI. The adjustments that parents do when they speak to children are similar across all three vocabulary groups; they use longer utterances than when speaking to adults, and respond faster to children than they do to other adults. However, overall pause duration varies with the vocabulary size of the children, and as a result durational aspects of the language environment to which the children are exposed differ between groups.

Neurodevelopment. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors.

The peripheral autonomic nervous system reaches far throughout the body and includes neurons of diverse functions, such as sympathetic and parasympathetic. We show that the parasympathetic system in mice--including trunk ganglia and the cranial ciliary, pterygopalatine, lingual, submandibular, and otic ganglia--arise from glial cells in nerves, not neural crest cells. The parasympathetic fate is induced in nerve-associated Schwann cell precursors at distal peripheral sites.

Detailed expression analysis of regulatory genes in the early developing human neural tube.

Studies in model organisms constitute the basis of our understanding of the principal molecular mechanisms of cell fate determination in the developing central nervous system. Considering the emergent applications in stem cell-based regenerative medicine, it is important to demonstrate conservation of subtype specific gene expression programs in human as compared to model vertebrates. We have examined the expression patterns of key regulatory genes in neural progenitor cells and their neuronal and glial descendants in the developing human spinal cord, hindbrain, and midbrain, and compared these with developing mouse and chicken embryos.

A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning.

The deployment of morphogen gradients is a core strategy to establish cell diversity in developing tissues, but little is known about how small differences in the concentration of extracellular signals are translated into robust patterning output in responding cells. We have examined the activity of homeodomain proteins, which are presumed to operate downstream of graded Shh signaling in neural patterning, and describe a feedback circuit between the Shh pathway and homeodomain transcription factors that establishes non-graded regulation of Shh signaling activity. Nkx2 proteins intrinsically strengthen Shh responses in a feed-forward amplification and are required for ventral floor plate and p3 progenitor fates.

Control of Notch-ligand endocytosis by ligand-receptor interaction.

In Notch signaling, cell-bound ligands activate Notch receptors on juxtaposed cells, but the relationship between ligand endocytosis, ubiquitylation and ligand-receptor interaction remains poorly understood. To study the specific role of ligand-receptor interaction, we identified a missense mutant of the Notch ligand Jagged1 (Nodder, Ndr) that failed to interact with Notch receptors, but retained a cellular distribution that was similar to wild-type Jagged1 (Jagged1(WT)) in the absence of active Notch signaling. Both Jagged1(WT) and Jagged1(Ndr) interacted with the E3 ubiquitin ligase Mind bomb, but only Jagged1(WT) showed enhanced ubiquitylation after co-culture with cells expressing Notch receptor.

Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression.

Homeodomain (HD) transcription factors and components of the Notch pathway [Delta1 (Dll1), Jagged1 (Jag1) and the Fringe (Fng) proteins] are expressed in distinct progenitor domains along the dorsoventral (DV) axis of the developing spinal cord. However, the internal relationship between these two regulatory pathways has not been established. In this report we show that HD proteins act upstream of Notch signalling.

Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells.

Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons.

Lmx1b is essential for the development of serotonergic neurons.

The specification and differentiation of serotonergic (5-HT) neurons require both extrinsic signaling molecules and intrinsic transcription factors to work in concert or in cascade. Here we identify the genetic cascades that control the specification and differentiation of 5-HT neurons in mice. A major determinant in the cascades is an LIM homeodomain-containing gene, Lmx1b, which is required for the development of all 5-HT neurons in the central nervous system.