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. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts

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). These two structures are found in close proximity to the kidneys and dorsal aorta, in a region where paraganglioma, pheochromocytoma and neuroblastoma originate in the majority of clinical cases. Recent studies showed that the chromaffin cells comprising the adrenal medulla are largely derived from nerve-associated multipotent Schwann cell precursors (SCPs) arriving at the adrenal anlage with the preganglionic nerve fibers, whereas the migratory neural crest cells provide only minor contribution. However, the embryonic origin of the ZO, which differs from the adrenal medulla in a number of aspects, has not been studied in detail. The ZO is composed of chromaffin cells in direct contact with the dorsal aorta and the intraperitoneal cavity and disappears through an autophagy-mediated mechanism after birth. In contrast, the adrenal medulla remains throughout the entire life and furthermore, is covered by the adrenal cortex. Using a combination of lineage tracing strategies with nerve- and cell type-specific ablations, we reveal that the ZO is largely SCP-derived and forms in synchrony with progressively increasing innervation. Moreover, the ZO develops hand-in-hand with the adjacent sympathetic ganglia that coalesce around the dorsal aorta. Finally, we were able to provide evidence for a SCP-contribution to a small but significant proportion of sympathetic neurons of the posterior paraganglia. Thus, this cellular source complements the neural crest, which acts as a main source of sympathetic neurons. Our discovery of a nerve-dependent origin of chromaffin cells and some sympathoblasts may help to understand the origin of pheochromocytoma, paraganglioma and neuroblastoma, all of which are currently thought to be derived from the neural crest or committed sympathoadrenal precursors

Turn-taking and early phonology : Contingency in parent-child interaction and assessment of early speech production

This thesis focuses on contingency in parent-child interaction, investigating it in the light of the linguistic capacity of the child and the status of the caregiver. Further, the thesis covers the development of two tools to assess the developmental maturity level of expressive phonology. A functional emergentist perspective on language acquisition is taken, which includes a phonetic perspective on phonological development. Both infant language development and factors that influence parent responsiveness are explored.  The thesis contains four studies. In the first study, durations of parents’ utterances and pauses in interaction with their 18-month-old infants were related to the infant’s vocabulary size. Recordings of interactions of fifteen children and their parents were made at home in daily life situations. The children were divided into three groups according to their vocabulary size: large, typical or small. The main finding is that parents in the large vocabulary size group responded faster to their children compared to the parents in the typical size vocabulary group, who in turn responded faster than the parents in the small vocabulary size group.  In study two, duration in vocal turn-taking between 6-month old infants and their caregivers was investigated, in terms of the status of the caregiver and the sex of the infant. Caregivers’ pauses were measured in 10-minute caregiver-infant interactions recorded at home. It was found that primary caregivers responded faster to their infants compared to secondary caregivers, and that in turn, infants responded faster to the primary caregiver than to the secondary caregiver.  Study three introduces the Word Complexity Measure for Swedish (WCM-SE), a tool for calculating phonological complexity in words or utterances. Calculations are based on ten parameters describing speech structures that are considered phonetically complex to produce. In the development of  the WCM-SE, both language-specific and language-general descriptions of speech development were considered, as well as universal acoustic and aerodynamic principles.  Study four documents the selection of Swedish words for the word lists in the test Profiles of Early Expressive Phonological Skills for Swedish (PEEPS-SE). The selection was based on criteria of age of acquisition and word complexity, as measured by the WCM-SE.  The findings presented in this thesis contribute to our knowledge of early interaction and parents’ potential impact on the child’s early language and communication development. Further, the tools developed for the assessment of Swedish are valuable contributions both to the research field of early phonology and to clinical work in Sweden. At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.</p

Regional control of cell fate determination and neurogenesis in the developing CNS

The development of a functional central nervous system relies on the generation of distinct neuronal subtypes in a spatially and temporally defined order. The spatial organisation is achieved at early developmental time points when neural progenitor cells encounter fields of secreted morphogenic signalling molecules along the anterioposterior and dorsoventral axes of the embryo. Translation of these gradients into distinct expression patterns of determinant genes leads to the establishment of molecularly defined progenitor domains, each producing a specific type of neuron. The process of neurogenesis through which progenitor cells differentiate into maturing neurons is tightly regulated. Proneural genes promote neurogenesis, whereas Notch signalling counteracts this activity to ensure a balance between the numbers of progenitor cells and neurons. One of the challenges in the field of developmental neuroscience, and the main subject of this thesis, is to unravel the molecular cascades that underlie the differentiation programmes of distinct types of neurons. In paper I and II we identify key components of the midbrain dopaminergic (mDA) and hindbrain serotonergic (5-HT) differentiation pathways. mDA and 5-HT neurons are clinically relevant cell types as the degeneration of mDA cells is the major hallmark of Parkinsons s disease, and dysregulation of 5-HT homeostasis has been associated with a number of disorders including autism, schizophrenia, and drug addiction. In paper I we propose that the transcription factors Lmx1a and Msx1/2 are important for the acquisition of the mDA cell fate by suppressing alternative cell fates, promoting the progression of neurogenesis, and inducing expression of mDA specific marker genes. Moreover, we find that Lmx1a has the ability to direct differentiating embryonic stem cells into mDA neurons, an approach that may be instrumental in the development of cell replacement strategies for the treatment of patients with Parkinson s disease. In Paper II we identify the transcription factor Lmx1b as an early postmitotic marker of 5-HT neurons. We provide evidence that Lmx1b acts as an intermediate determinant in the serotonergic differentiation programme downstream of the progenitor marker Nkx2.2 but upstream of neurotransmitter expression. In paper III we construct a comprehensive human atlas of the developmental expression of molecules that have previously been implicated in neuronal and glial patterning, specification and differentiation in common model organisms. We find that the majority of the developmentally important genes found in model organisms show a conserved expression pattern in human suggesting preserved molecular mechanisms, thus validating the use of model organisms to understand human development and disease. Nevertheless, a few deviations were observed, emphasising the importance of such comparisons. In paper IV we investigate the control and functional rationale behind the regional expression of the Notch ligands, Dll1 and Jag1, in the developing spinal cord. We find that the patterning genes which govern cell fate determination also delimit the expression of these Notch ligands into distinct progenitor domains. Furthermore, a similar expression control of the Notch-modifying Fringe genes prevents Notch signalling across borders between Dll1+ and Jag1+ domains. We surmise that these two levels of signalling regulation ensure a domain specific control of neurogenesis which may be important to make sure that the correct numbers of each neuronal subtype are generated in the developing spinal cord

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. Articulatory adaptation toward hyperarticulation is quantified as difference in vowel space area between IDS and adult-directed speech (ADS). Phonetic complexity is estimated using the Word Complexity Measure for Swedish (WCM-SE). The results show that vowels in IDS was more hyperarticulated than vowels in ADS, and that parents articulatory adaptation in terms of hyperarticulation correlates with phonetic complexity of infant vocalizations. This can be explained either by the parents articulatory behavior impacting the infants vocalization behavior, the infants social and communicative cues eliciting hyperarticulation in the parents speech, or the two variables being impacted by a third, underlying variable such as parents general communicative adaptiveness.Funding Agencies|Riksbankens Jubileumsfond [RJ P17-0175]; Marcus and Amalia Wallenberg Foundation [MAW 2011.0070]</p

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. Previous research has shown that on the level of subject means, a positive correlational relationship exists. However, the previous findings do not provide information about the directionality of that relationship. In this study the relationship is investigated on a conversational turn level, which makes it possible to draw conclusions on whether the behavior of the infant is impacting the parent, the behavior of the parent is impacting the infant, or both. Parent vowel hyperarticulation was quantified using the vhh-index, a measure that allows vowel hyperarticulation to be estimated for individual vowel tokens. Phonetic complexity of infant vocalizations was calculated using the Word Complexity Measure for Swedish. Findings were unexpected in that a negative relationship was found between parent vowel hyperarticulation and phonetic complexity of the immediately following infant vocalization. Directionality was suggested by the fact that no such relationship was found between infant phonetic complexity and vowel hyperarticulation of the immediately following parent utterance. A potential explanation for these results is that high degrees of vowel hyperarticulation either provides, or co-occurs with, large amounts of phonetic and/or linguistic information, which may occupy processing resources to an extent that affects production of the next vocalization

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. Previous research has shown that on the level of subject means, a positive correlational relationship exists. However, the previous findings do not provide information about the directionality of that relationship. In this study the relationship is investigated on a conversational turn level, which makes it possible to draw conclusions on whether the behavior of the infant is impacting the parent, the behavior of the parent is impacting the infant, or both. Parent vowel hyperarticulation was quantified using the vhh-index, a measure that allows vowel hyperarticulation to be estimated for individual vowel tokens. Phonetic complexity of infant vocalizations was calculated using the Word Complexity Measure for Swedish. Findings were unexpected in that a negative relationship was found between parent vowel hyperarticulation and phonetic complexity of the immediately following infant vocalization. Directionality was suggested by the fact that no such relationship was found between infant phonetic complexity and vowel hyperarticulation of the immediately following parent utterance. A potential explanation for these results is that high degrees of vowel hyperarticulation either provide, or co-occur with, large amounts of phonetic and/or linguistic information, which may occupy processing resources to an extent that affects production of the next vocalization.Funding Agencies|Riksbankens Jubileumsfond [RJ P17-0175]; Marcus and Amalia Wallenberg Foundation [MAW 2011.0070]</p

La oss snakke om seksualitet! : seksuell helse hos menn med kronsik hjertesvikt

Denne oppgaven tar for seg hvordan diagnosen kronisk hjertesvikt påvirker menns seksuelle helse både fysisk og psykisk. Vi ser på hvilken betydning det har for pasienten at sykepleier snakker om det grunnleggende behovet for seksualitet. Oppgaven er et litteraturstudie som bygger på selvvalgt litteratur, 7 forskningsartikler og 2 fagartikler. Ved å se på de ulike forskningsartiklene har vi fått kunnskap om seksualitetens betydning for pasienter med hjertesvikt og hvordan sykepleier forholder seg til dette. Funn fra forskning viser at pasienter med hjertesvikt har en lavere opplevelse av seksuell helse, og dårlig seksuell helse kan føre til angst, depresjon og et truet selvbilde. Hjertesviktpasienter ønsker spesifikk informasjon om hvordan sykdommen påvirker deres seksualitet, men sykepleiere er ikke komfortable med å snakke om dette. Sykepleiere forteller at de unngår temaet av hensyn til pasienten samt at de mangel på kunnskap. Mange sykepleiere angir at grunnutdanningen ikke formidler kunnskap om seksualitet eller seksuell helse. Vi har valgt å bruke Joyce Travelbee sin sykepleieteori gjennom oppgaven fordi hun vektlegger grunnutdanningens ansvar for å forme gode sykepleiere. Hun setter også pasientens opplevelse av helse i fokus og mener at helsehjelp skal ytes der pasienten opplever at hjelpen trengs, noe som er relevant for oppgaven. Funnene fra oppgaven viser at det er av betydning for menn med kronisk hjertesvikt at sykepleiere snakker om seksualitet. Både fysiske og psykiske aspekter ved seksualitet må inkluderes for å utføre holistisk sykepleie. Det er en sammenheng mellom selvbilde og seksuell helse. Pasienter med dårlig selvbilde har lavere grad av etterlevelse, noe som medfører hyppige reinnleggelser og dårligere sykdomsprognose. Seksuell helse er en individuell egenopplevelse og for noen kan det å ikke være seksuelt aktivt være helsefremmende

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. The relationship of early consonant production to number of words produced of both groups were examined and the phonological complexity of reported words was compared between the groups. The results showed that children with HL (n = 8) produced a similar number of words as the NH (n = 8) at 18 months, but fewer at 24 and 30 months. Hours of HA use showed significant correlations to number of words. The number of different true consonants at 18 months for the whole group showed a significant relationship to number of words produced at 24 months. No significant differences were found between children with HL and NH children regarding phonological complexity of reported words. The findings indicate that the children born with moderate HL who were fitted with hearing aids (HAs) before 6 months of age are at risk in their development of expressive vocabulary. Full-time use of HAs and monitoring of early consonant use should be encouraged in the early intervention of this target group.Funding Agencies|Wibelfonden; , Tysta skolan; Majblomman; Region Stockholm</p