The hair follicle is a source of epithelial stem cells and site of origin for several types of skin tumors. Although it is clear that follicles arise by way of a series of inductive tissue interactions, identification of the signaling molecules driving this process remains a major challenge in skin biology. In this study we report an obligatory role for the secreted morphogen Sonic hedgehog (Shh) during hair follicle development. Hair germs comprising epidermal placodes and associated dermal condensates were detected in both control and Shh -/- embryos, but progression through subsequent stages of follicle development was blocked in mutant skin. The expression of Gli1 and Ptc1 was reduced in Shh -/- dermal condensates and they failed to evolve into hair follicle papillae, suggesting that the adjacent mesenchyme is a critical target for placode-derived Shh. Despite the profound inhibition of hair follicle morphogenesis, late-stage follicle differentiation markers were detected in Shh -/- skin grafts, as well as cultured vibrissa explants treated with cyclopamine to block Shh signaling. Our findings reveal an essential role for Shh during hair follicle morphogenesis, where it is required for normal advancement beyond the hair germ stage of development.
We examined spoken sentence comprehension in school-age children with developmental dyslexia or language impairment (LI), compared to age-matched and younger controls. Sentence-picture matching tasks were employed under three different working memory (WM) loads, two levels of syntactic difficulty, and two sentence lengths. Phonological short-term memory (STM) skills and their relation to sentence comprehension performance were also examined. When WM load was minimized, the LI group performed more poorly on the sentence comprehension task compared to the age-matched control group and the dyslexic group. Across groups, sentence comprehension performance generally decreased as the WM load increased, but this effect was somewhat more pronounced in the dyslexic group compared to the age-matched group. Moreover, both the LI and dyslexic groups showed poor phonological STM compared to the age-matched control group, and a significant correlation was observed between phonological STM and sentence comprehension performance under demanding WM loads. The results indicate subtle sentence processing difficulties in dyslexia that might be explained as resulting from these children's phonological STM limitations.Children with developmental dyslexia fail to develop age appropriate reading skills despite normal-range nonverbal intelligence, adequate learning opportunities, and the absence of a frank neurological disorder (Snowling, 2000). Although dyslexia is by definition a reading disorder, there is a strong consensus that spoken language deficits also play a role in reading failure. Specifically, theories suggest that difficulties with phonological processing impair the ability to learn consistencies in the mapping between letters and sounds, which in turn, impacts the ability to efficiently read familiar and novel words (Bradley & Bryant, 1983;
We examined categorical speech perception in school-age children with developmental dyslexia or Specific Language Impairment (SLI), compared to age-matched and younger controls. Stimuli consisted of synthetic speech tokens in which place of articulation varied from 'b' to 'd'. Children were tested on categorization, categorization in noise, and discrimination. Phonological awareness skills were also assessed to examine whether these correlated with speech perception measures. We observed similarly good baseline categorization rates across all groups; however, when noise was added, the SLI group showed impaired categorization relative to controls, whereas dyslexic children showed an intact profile. The SLI group showed poorer than expected between-category discrimination rates, whereas this pattern was only marginal in the dyslexic group. Impaired phonological awareness profiles were observed in both the SLI and dyslexic groups; however, correlations between phonological awareness and speech perception scores were not significant. The results of the study suggest that in children with language and reading impairments, there is a significant relationship between receptive language and speech perception, there is at best a weak relationship between reading and speech perception, and indeed the relationship between phonological and speech perception deficits is highly complex.
We used event-related potentials (ERPs) to compare auditory word recognition in children with specific language impairment (SLI group; N=14) to a group of typically developing children (TD group; N=14). Subjects were presented with pictures of items and heard auditory words that either matched or mismatched the pictures. Mismatches overlapped expected words in word-onset (cohort mismatches; see: DOLL, hear: dog), rhyme (CONE -bone), or were unrelated (SHELL -mug). In match trials, the SLI group showed a different pattern of N100 responses to auditory stimuli compared to the TD group, indicative of early auditory processing differences in SLI. However, the phonological mapping negativity (PMN) response to mismatching items was comparable across groups, suggesting that just like TD children, children with SLI are capable of establishing phonological expectations and detecting violations of these expectations in an online fashion. Perhaps most importantly, we observed a lack of attenuation of the N400 for rhyming words in the SLI group, which suggests that either these children were not as sensitive to rhyme similarity as their typically developing peers, or did not suppress lexical alternatives to the same extent. These findings help shed light on the underlying deficits responsible for SLI.
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