Browsing by Subject "Speech"
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Item Cell Type-Specific Roles of FoxP Transcription Factors in Vocalization and Cognition(2019-07-23) Co, Marissa; Tsai, Peter; Konopka, Genevieve; Johnson, Jane E.; Roberts, ToddMutations of the forkhead domain transcription factors FOXP2 and FOXP1 are highly associated with neurodevelopmental disorders affecting speech and language. Across vertebrate species, their conserved expression patterns in the developing and adult brain predict important functions in neural circuits mediating vocalization and sensorimotor learning. Their known gene targets regulate neuronal development, activity, and plasticity, and animal models of FoxP2 and FoxP1 function have linked some of these molecular functions with neurophysiological and behavioral phenotypes. Still, much remains unknown about molecular networks in the brain driven by these transcription factors, especially in specific regions and cell types. During my dissertation work, I sought to elucidate FoxP2 and FoxP1 functions in cortical, striatal, and cerebellar neurons in mice and zebra finches. This approach of combining comparative genomics with functional studies of salient genes has proven a powerful method for understanding higher cognitive functions such as language (Chapter Two). By characterizing mice lacking cortical Foxp2, I identified its roles in dopamine signaling, interneuron development, and cognitive behavior, but surprisingly not in vocalization (Chapter Three). I further studied the interaction between FoxP2 and its cortical binding partner TBR1, and I found synergistic gene regulation by these transcription factors in neural cells (Chapter Four). I contributed to identification of roles for cortico-hippocampal FoxP1 in cortical development and vocalization (Chapter Five), as well as roles for cerebellar FoxP2 in Purkinje cell morphology, vocalization, and gross motor function (Chapter Six). Finally, I generated tools and datasets to further our understanding of corticostriatal functions of FoxP2 and FoxP1 in vocal learning zebra finches (Chapter Seven). In light of these studies, I discuss their implications for understanding human disorders affecting speech and language, and I impart further hypotheses and recommendations for continuing their study (Chapter Eight). Together, these findings contribute to our knowledge of conserved roles for FoxP2 and FoxP1 in vocal behavior and cognition.Item [Southwestern News](2005-10-03) McKenzie, AlineItem [Southwestern News](2001-09-07) Baxter, MindyItem Speech and Language Performance of 3 Year Old Children Born Preterm: A Preliminary Report(2013-01-22) Seidel, Laurie; Cobbs, Anna; Regetz, Catherine; Heyne, Roy; Tobey, Emily; Campbell, Thomas; Weinberger, DebraINTRODUCTION: The association between preterm birth and an increased risk for cognitive impairment and academic struggles later in life is well established. In particular, the tendency for preterm infants to show delayed language acquisition even without evidence of brain damage has been the subject of much recent research. We hypothesized there would be a positive association between birth weight/gestational age of preterm infants and their speech and language performance at 3 years of age. METHODS: We recruited 43 children from the Low Birth Weight Clinic at Children's Medical Center Dallas and the Pediatrix Tots Clinic at Baylor University Medical Center with a mean age of 37.8 months (range 36-45 months). Their mean gestational age was 28.6 weeks (range 23-35 weeks) and mean birth weight was 1219.8 grams (range 550-2525 grams). Children had no history of hearing loss, structural abnormalities such as cleft lip or palate, or prolonged mechanical ventilation after NICU discharge. Each child underwent a hearing screening, the Battelle Developmental Inventory Screening Test, and 40 of the 43 children underwent the Goldman-Fristoe 2 Test of Articulation (GFTA). Each child's spontaneous speech was recorded during a 30-minute interactive play session with their primary caregiver. Their speech was then transcribed and analyzed using the Systematic Analysis of Language Transcripts (SALT) program, matching each participant to a group of control children based on age and gender. SALT measures included percent intelligibility, total number of words, number of different words, and words per minute. Finally, the primary caregiver completed the MacArthur-Bates Communicative Development Inventory-III for each child. RESULTS: Performance on the MacArthur-Bates and SALT measures did not correlate with birth weight or gestational age. SALT analysis showed that our participants produced significantly shorter utterances, did not use as many different words, and were significantly less intelligible than controls. The mean age equivalent on the Battelle was 36.3 months (range 14-51 months). DISCUSSION: Preliminary analysis does not support a correlation between birth weight/gestational age of preterm infants and speech and language performance at age 3 years. Therefore, a higher birth weight or later gestational age does not imply a lesser risk for preterm infants. Thus, it is critically important that parents and pediatricians alike remain vigilant when assessing the speech and language of all children who were born preterm, regardless of birth weight or gestational age.Item Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development(2018-07-30) Hickey, Stephanie Lepp; Roberts, Todd; Powell, Craig M.; Huber, Kimberly M.; Takahashi, JosephDuring my dissertation work I sought to better understand the conserved and human-specific functions of FoxP2. Intrigued by the enrichment of FOXP2 in the human subplate layer, I hypothesized that FOXP2 regulates evolutionarily distinct subplate gene expression patterns and tested this theory by performing RNA-seq in human differentiating neurons and leveraging publically available developmental expression data from human, macaque, and mouse cortex in order to identify human specific, primate specific, and conserved subplate genes regulated by FOXP2. This study not only identified human specific targets in this expanded, transient region, but it may also inspire research of the conserved, non-cell-autonomous role of FoxP2 in the maturation of thalamocortical circuitry. Additionally, I performed ChIP-seq and RNA-seq in human neural progenitor cells and found evidence that FOXP2 may actively modify the chromatin landscape. This lead me to hypothesize that by modifying the chromatin landscape of neural progenitors FOXP2 turns off cellular programs that maintain an undifferentiated state while turning on programs that drive a cell towards a neuronal fate. To test this hypothesis, I identified areas of nucleosomal depletion using ATAC-seq and correlated epigenetic changes caused by FOXP2 expression to changes in gene expression in proliferating and differentiating human neurons. This allowed me to define two separate molecular mechanisms by which FOXP2 regulates gene expression in human neurons, even finding a potential FOXP2 co-activator. Together, these studies push forward our understanding of the function of FoxP2, especially in human neurons, and provide a source of data from which the next hypotheses concerning FoxP2 and human language formation may be derived.Item [UT News](1987-09-03) McVay, Ann